Molecular Science in Oral-Systemic Medicine

~Autumn Seminar~

東京医科歯科大学

第7回グローバルCOE国際シンポジウム

Tokyo Medical and Dental UniversityThe 7th Global COE International Symposium

November 12th~14th, 2012Tokyo Medical andDental University

http://www.tmd.ac.jp/cmn/gcoe/index.html Fifth Retreat Meeting

グローバルCOEプログラム歯と骨の分子疾患科学の国際教育研究拠点

デント・メドミクスのインテリジェンスハブ

Organizing Chairs of The 7th Global COE International Symposium

Yuichi Izumi, Professor and chairman, Dept. of Periodontology

Keiji Moriyama, Professor and chairman, Dept. of Maxillofacial Orthognathics

Molecular Science in Oral-Systemic Medicine - Autumn Seminar -

November 12th~14th, 2012

2012.11.12（Mon）

13：00 − 13：10 PresidentAddress Takashi Ohyama

Session 1 chairpersons : Irma Thesleff, Keiji Moriyama

13：10 − 14：10 Martha J. Somerman NIDCR/NIH:Today'sDiscovery,Tomorrow'sCure

14：10 − 15：10 Peter A. Mossey Aglobalapproachtothechallengeoforofacialclefting

15：10 − 15：40 PosterSession1（CoffeeBreak）

Session 2 chairpersons : Peter A. Mossey, Masaki Noda

15：40 − 16：40 Kenjiro Kosaki Clinicalmoleculardiagnosticsofcongenitalmalformationsyndrome usingin-solutionhybridization-basedenrichmentandmassively parallelsequencing

16：40 − 17：40 Lynda F. Bonewald TheOsteocyteasaRegulatorofBoneRemodeling

17：40 − 18：40 Keiji Moriyama Newbiologicalinsightsoftoothmovementinresponsetomechanical stress

19：00 − Reception

2012.11.13（Tue）

Session 3 chairpersons : Martha J Somerman, Akira Yamaguchi

9：00 − 10：00 Irma Thesleff Mechanismsoftoothrenewal

10：00 − 11：00 Satoshi Fukumoto Roleofdentalepithelium-stemcellinteractionsduringdentalcell differentiation

11：00 − 11：10 CoffeeBreak

Session 4 chairpersons : Linda F. Bonewald, Satoshi Fukumoto

11：10 − 12：10 Takashi Tsuji ToothRegenerativeTherapyasaFutureDentalTreatment

12：10 − 12：40 Naoto Haruyama Amelogenins:Multifacetedenamelmatrixproteinsinhardtissuebiology

Session 5 chairpersons : Young Ku, Kazuhisa Yamazaki

13：40 − 14：40 Gregory J. Seymour Theperiodontal-systemicconnection:Molecularmechanismsand theirsignificanceinoverallhealthcare

14：40 − 15：40 Nawarat Wara-aswapati Oral-SystemicConnection:RolesoftheHostFactors

15：40 − 16：10 PosterSession2（CoffeeBreak）

Session 6 chairpersons : Nawarat Wara-aswapati, Yuichi Izumi

16：10 − 17：10 Young Ku Thebiologiceffectofoligopeptidesderivedfromfibronectinandits applicationtobiomimetics

17：10 − 18：10 Kazuhisa Yamazaki Periodontaldiseaseandatherothromboticdiseases:Lessonsfrom clinicalandbasicstudies

2012.11.14（Wed）

Session 7 chairpersons : Young−Chel Park, Takashi Ono

10：00 − 11：00 Tetsu Takahashi Paradigmshiftoforhthognathicsurgeryindiagnosis,simulation,and guidedsurgery

11：00 − 12：00 Seung-Hak Baek RecentParadigmChangeinThree-DimensionalImagingand CAD-CAMTechnologyforVirtualOrthodonticTreatmentand OrthognathicSurgery

Session 8 chairpersons : Seung−Hak Baek, Tetsu Takahashi

13：00 − 14：00 Young-Chel Park Clinicalandbiomechanicalconsiderationsforcorrectionofthedento- facialdeformities

14：00 − 15：00 Kiyoshi Harada OrthognathicSurgery:TheConsiderationsforitsAccuracyand Safety

15：00 ClosingRemarkYuichiIzumi Adjourn

C O N T E N T SMartha J. Somerman ………………………………………………………… 1NIDCR/NIH:Today'sDiscovery,Tomorrow'sCure

Peter A. Mossey ……………………………………………………………… 5Aglobalapproachtothechallengeoforofacialclefting

Kenjiro Kosaki………………………………………………………………… 9Clinicalmoleculardiagnosticsofcongenitalmalformationsyndromeusingin-solutionhybridization-basedenrichmentandmassivelyparallelsequencing

Lynda F. Bonewald………………………………………………………… 13TheOsteocyteasaRegulatorofBoneRemodeling

Keiji Moriyama……………………………………………………………… 17Newbiologicalinsightsoftoothmovementinresponsetomechanicalstress

Irma Thesleff………………………………………………………………… 21Mechanismsoftoothrenewal

Satoshi Fukumoto ………………………………………………………… 25Roleofdentalepithelium-stemcellinteractionsduringdentalcelldifferentiation

Takashi Tsuji………………………………………………………………… 29ToothRegenerativeTherapyasaFutureDentalTreatment

Naoto Haruyama…………………………………………………………… 33Amelogenins:Multifacetedenamelmatrixproteinsinhardtissuebiology

Gregory J. Seymour………………………………………………………… 37Theperiodontal-systemicconnection:Molecularmechanismsandtheirsignificanceinoverallhealthcare

Nawarat Wara-aswapati…………………………………………………… 41Oral-SystemicConnection:RolesoftheHostFactors

Young Ku …………………………………………………………………… 45Thebiologiceffectofoligopeptidesderivedfromfibronectinanditsapplicationtobiomimetics

Kazuhisa Yamazaki………………………………………………………… 49Periodontaldiseaseandatherothromboticdiseases:Lessonsfromclinicalandbasicstudies

Tetsu Takahashi …………………………………………………………… 53Paradigmshiftoforhthognathicsurgeryindiagnosis,simulation,andguidedsurgery

Seung-Hak Baek…………………………………………………………… 57RecentParadigmChangeinThree-DimensionalImagingandCAD-CAMTechnologyforVirtualOrthodonticTreatmentandOrthognathicSurgery

Young-Chel Park…………………………………………………………… 61Clinicalandbiomechanicalconsiderationsforcorrectionofthedento-facialdeformities

Kiyoshi Harada……………………………………………………………… 65OrthognathicSurgery:TheConsiderationsforitsAccuracyandSafety

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NIDCR/NIH: Today's Discovery, Tomorrow's Cure

Martha J. Somerman D.D.S., Ph.D.

DirectorNIDCR,NIHandChiefLaboratoryforOralConnectiveTissueBiology,NIAMS,NIH.Bethesda,Maryland

ThispresentationwillfocusonresearchsupportedbyNationalInstituteofDentaland

CraniofacialResearch/NationalInstitutesofHealth,withanemphasisonadvancesmade

towardimprovementsintreatmentofdental-oral-craniofacialpathologies/conditions.Research

topics,frombasictotranslationaltoclinical,willinclude:a)currentandplannedgenomic

analysis/genomicwideassociationstudiesappliedtoanalysisofdental-oral-craniofacial

pathologies/anomalies/disordersandwillincludecleftlip/palate,cariesandperiodontaldiseases

andSjogren’sSyndrome;b)salivarydiagnosticsfororal-systemicdiseases;c)oralcancerfrom

theoralcancergenomeprojecttoassaysfordiagnosisandearlydetectionofheadandneck

cancer;d)publichealthchallenges,e.g.,acute/chronicpainlinkedtotemporomandibularjoint

disordersandassociatedco-morbiditiesandhumanpapillomavirus-relatedoralcancers;e)

Themicrobiomeproject,wheredatahavebeenobtainedbysampling6sites(nasalpassages,

gastrointestinaltract,urogenitaltract,skinandoralcavity(9sites))andarebeinganalyzed

fortheroleofthesemicrobesinhumanhealthanddisease;andf)clinicalresearchwithinthe

clinicalresearchcenteratNIHandalsonationally/internationally.Theemphasiswillbeon

advancesinresearchsupportedbyNIDCR/NIHthathaveandwillcontinuetoimprovethe

qualityofhealthforallcommunities.

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CURRICULUM VITAE

Education

1968 NewYorkUniversity,ArtsandScience;BA1972 HunterCollege,InstituteofEnvironmentalHealth

Sciences,NewYork,NY;MS1975 NewYorkUniversity,CollegeofDentistry,NewYork,

NY;DDS1978 EastmanDentalResearchCenter,Rochester,NY;

CertificateinPeriodontology1980 DepartmentofPharmacology&Toxicology,University

ofRochesterMedicalCenter&DentalSchool,Rochester,NY;PhD

Position

2001-2002 AssociateDeanforResearch,Universityof Michigan,SchoolofDentistry2002-2011 Professor,UniversityofWashingtonSchoolof Dentistry,DepartmentofPeriodontics2002-2011 Dean,UniversityofWashingtonSchoolof Dentistry2003-2011 AdjunctProfessor,UniversityofWashington SchoolofDentistry,DepartmentofOralBiology2004-2011 AssociateMedicalStaff,Universityof WashingtonMedicalCenter2004-2011 MedicalStaff,SeattleCancerCareAlliance2004-2011 AssociateMedicalStaff,HarborviewMedical Center2011–present AffiliateProfessor,UniversityofWashington SchoolofDentistry,DepartmentofPeriodontics2011–present DeanEmeritus,UniversityofWashington, SchoolofDentistry

Award and Honors

2000 President-Elect,AADR2001 President,AADR2001 Fellow,AmericanAssociationfortheAdvancementof Science2003 WilliamJ.GiesAwardinPeriodontology2005 IADRDistinguishedScientist-ResearchinOralBiology Award2005 Fellow,PierreFauchardAcademy2006 Fellow,AmericanCollegeofDentists2006 Fellow,InternationalCollegeofDentists2008 AdvocacyAward,SeattleLocalChapter,American StudentDentalAssociation2010 HonoraryProfessorofWestChinaCollegeof Stomatology,SichuanUniversity2010 IADR/StraumannAwardinRegenerativePeriodontal Medicine2011 PaulGoldhaberAward,HarvardSchoolofDental Medicine2012 NewYorkUniversity,CollegeofDentistryDistinguished ScientistAward

Publications

PopowicsT,FosterBL,SwansonEC,FongHK,Somerman1.MJ.Definingtherootsofcementumformation.CellsTissuesOrgans181(3-4):248-57,2005.FosterBL,SomermanMJ.RegeneratingthePeriodontium:2.Isthereamagicformula?OrthodonticsandCraniofacialResearch8(4):285-91,2005.BerryJE,EalbaEL,PettwayGJ,DattaNS,SwansonEC,3.SomermanMJ,McCauleyLK.JunBasadownstreammediatorofPTHrPactionsincementoblasts.JournalofBoneandMineralResearch21(2):246-257,2006.HakkiSS,WangD,FranceschiRT,SomermanMJ.Bone4.SialoproteinGeneTransfertoPeriodontalLigamentCellsMayNotBeSufficienttoPromoteMineralizationInVitroorInVivo.JPeriodontol,77:167-173,2006.FosterBL,NocitiFH,SwansonEC,Matsa-DunnD,Berry5.JE,CuppCJ,ZhangP,SomermanMJ.RegulationofCementoblastGeneExpressionbyInorganicPhosphate,InVitro.CalcifTissueInt.78:103-112,2006.SwansonEC,FongHK,FosterBL,PaineML,Gibson6.CW,SneadML,SomermanMJ.Amelogeninsregulateexpressionofgenesassociatedwithcementoblastsinvitro.EurJOralSci114Suppl1:239-43,2006.RutherfordR,FosterBL,BammlerT,BeyerD,Sato7.S,SomermanMJ.ExtracellularPhosphateAltersCementoblastGeneExpression.JournalofDentalResearch85(6):505-509,2006.WooKM,JunJH,ChenVJ,SeoJ,BaekJH,RyooHM,8.KimGS,SomermanMJ,MaPX.Nano-fibrousscaffoldingpromotesosteoblastdifferentiationandbiomineralization.Biomaterials28:335-343,2006.NemotoE,DarveauRP,FosterBL,Nogueira-FilhoGR,9.SomermanMJ.RegulationofcementoblastfunctionbyP.gingivalislipopolysaccharideviaTLR2.JournalofDentalResearch85(8):733-738,2006.MadaY,MiyauchiM,OkaH,KitagawaM,Sakamoto10.K,IizukaS,SatoS,NoguchiK,SomermanMJ,TakataT.EffectsofendogenousandexogenousprostaglandinE2ontheproliferationanddifferentiationofamousecementoblastcellline(OCCM-30).J.Periodontol.200677(12):2051-8,Dec2006.ZhangH,SomermanMJ,BergJ,CunninghamML,Williams11.B.Dentalanomaliesinachildwithcraniometaphysialdysplasia.PediatrDent.2007Sep-Oct;29(5):415-9.NoguchiK,MiyauchiM,OkaH,KomakiM,SomermanMJ,12.TakataT.Cyclooxygenase-2-dependentprostaglandinE(2)upregulatesinterleukin(IL)-1alpha-inducedIL-6generationinmousecementoblasts.JPeriodontol.2007Jan;78(1):135-40.OkaH,MiyauchiM,SakamotoK,MoriwakiS,NiidaS,13.NoguchiK,SomermanMJ,TakataT.PGE2activatescementoclastogenesisbycementoblastsviaEP4.JDentRes.2007Oct;86(10):974-9.SatoS,KitagawaM,SakamotoK,IizukaS,KudoY,14.

Martha J. Somerman

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OgawaI,MiyauchiM,ChuEY,FosterBL,SomermanMJ,TakataT.Enamelmatrixderivativeexhibitsanti-inflammationpropertiesinmonocytes.JPeriodontol79(3)535-540,2008.OsathanonT,LinnesML,RajacharRM,RatnerBD,15.SomermanMJ,GiachelliCM.Microporousnanofibrousfibrin-basedscaffoldsforbonetissueengineering.Biomaterials294091-4099,2008.FatheraziS,Matsa-DunnD,RutherfordB,Foster16.B,SomermanMJ,PreslandR.Phosphateregulatesosteopontingenetranscription.JDentRes88(1):39-44,January2009.NagatomoKJ,TompkinsKA,FongH,ZhangH,FosterBL,17.ChuEY,MurakamiA,StadmeyerL,CanalisE,SomermanMJ.Transgenicoverexpressionofgremlinresultsindevelopmentaldefectsinenamelanddentininmice.JournalConnectiveTissueResearch49:6,391-400,2008.FongH,FosterBL,SarikayaM,SomermanMJ.Structure18.andmechanicalpropertiesofAnk/Ankmutantmousedentaltissues–Ananimalmodelforstudyingperiodontalregeneration.ArchOralBiol.54(6):570-576,6/09.NemotoE,KoshikawaY,KanayaS,TsuchiyaM,Tamura19.M,SomermanMJ,ShimauchiH.Wntsignalinginhibitscementoblastdifferentiationandpromotesproliferation.Bone44:805-812,2009.OsathanonT,GiachelliCM,SomermanMJ.Immobilization20.ofAlkalinePhosphataseonMicroporousNanofibrousFibrinScaffoldsforBoneTissueEngineering.Biomaterials304513-4521,2009FongH,ChuEY,TompkinsKA,FosterBL,Nociti21.FH,SitaraD,LanskeB,andSomermanMJ.AberrantcementumphenotypeassociatedwithhypophoshphatemicHypmouse.JPeriodontol,80:1348-54,2009.LeeM,ChuE,El-AbbadiM,FosterB,TompkinsK,22.GiachelliC,SomermanM.CharacterizationofMandibularBoneinaMouseModelofChronicKidneyDisease.JPeriodotol,81:300-309,2010.ChuEY,FongH,BlethenFA,TompkinsKA,Foster23.BF,YehKD,NagatomoKJ,D.Matsa-DunnD,SitaraD,LanskeB,RutherfordRB,andSomermanMJ.Ablationofsystemicphosphateregulatinggenefibroblastgrowthfactor23(Fgf23)compromisesthedentoalveolarcomplexAnatomicalRecord,293:1214-1226,2010.ZhangH,TompkinsK,GarriguesJ,SneadML,Gibson24.C,SomermanMJ.FullLengthAmelogeninBindstoCellSurfaceLAMP-1onToothRoot/PeriodontiumAssociatedCells.ArchOralBio,55(6):417-4252010.KanayaS,NemotoE,EbeY,SomermanM,andShimauchi25.H.Elevatedextracellularcalciumincreasesfibroblastgrowthfactor-2geneandproteinexpressionlevelsviaacAMP/PKAdependentpathwayincementoblasts.Bone,Sep;47(3):564-72,2010.HakkiSS,FosterBL,NagatomoKK,BozkurtSB,Hakki26.EE,SomermanMJ,andNohutcuRM.Bonemorphogenetic

Protein-7enhancescementoblastfunction,invitro.JPeriodotol,81(11):1663-1674,2010.BallwegR,BergJ,DeRouenT,FisetL,MouradianW,27.SomermanM.DentalEducationintheUnitedStates:ExpandingourpartnershipsbeyondtheFourWalls.JDentEduc.75:300-309,2011.SomermanMJ.GrowthFactorsandPeriodontal28.Engineering-wherenext?JDentRes,90(1):7-8,2011.FosterBL,NagatomoKJ,BamashmousSO,Tompkins29.KA,FongH,DunnD,ChuEY,GuenterC,KingsleyDM,RutherfordRBandSomermanMJ.TheProgressiveAnkylosisProteinRegulatesCementumAppositionandExtracellularMatrixComposition.CellsTissuesOrgans,194(5):382-405,2011.TadaH,NemotoE,FosterBL,SomermanMJ,and30.ShimauchiH.Phosphateincreasesbonemorphogeneticprotein-2expressionthroughcAMP-dependentproteinkinaseandERK1/2pathwaysinhumandentalpulpcells.JBoneMineralRes,48(6):1409-1416,2011.RodriguesTL,NagatomoKJ,FosterBL,NocitiFH,Jr.,and31.SomermanMJ.Modulationofphosphate/pyrophosphatemetabolismtoregeneratetheperiodontium.Anovelinvivoapproach.JPeriodontol,82:1757-1766,2011.Rodrigues,TL,FosterBL,SilverioKG,Luciane,M,Casati32.MZ,SallumEA,SomermanMJ,NocitiFH.Correctionofhypophospatasia(Hpp)associatedmineralizationdeficienciesinvitrobyphosphate/prophosphatemodulationinperiodontalligamentcells.JPeriodontol.83(5):653-663,2012.SilverioK,DavidsonK,JamesR,AdamsA,FosterBL,33.NocitiF,SomermanMJ,andMoonR.TheWnt/ β-cateninpathwayregulatesBmp2-mediateddifferentiationofdentalfolliclecellsalongacementoblast/osteoblastpathway.JournalofPeriodontalResearch,47(3):309-312,2012.CaoZ,ZhangH,ZhouX,HanX,RenY,GaoT,Xiao34.Yin,deCrombruggheB,SomermanMJ,andFengJQ.GeneticEvidencefortheVitalFunctionofOsterixinCementogenesis.JBoneandMineralResearch:5,1080-1092,2012.SunJ,OrapinH,BumgarnerR,LakelyB,SomermanMJ35.andZhangH.Lasercapturemicrodissection(LCM)enablescellularandmolecularstudiesoftoothrootdevelopment.InternationalJournalofOralSciences,4,7-13,2012.FosterBL,NagatomoKJ,NocitiFH,FongH,DunnD,36.TranAB,WangW,NarisawaS,MillánJL,andSomermanMJ.Centralroleofpyrophosphateinacellularcementum.,PLoSONE,7(6),e38393,2012.RodriguesTL,FosterBL,SilverioKG,MartinsL,37.CasatiMZ,SallumEA,SomermanMJ,NocitiFH.Hypophosphatasia-associateddeficienciesinmineralizationandgeneexpressionincultureddentalpulpcellsobtainedfromhumanteeth..JEndodontics:38(7):907-912,2012.

Martha J. Somerman

4

M E M O

5

A global approach to the challenge of orofacial clefting

Peter A. Mossey, B.D.S., Ph.D.

ProfessorofCraniofacialDevelopmentandDentofacialOrthopaedics,UniversityofDundee

Background:Birthdefectsingeneralandcraniofacialanomalies,themostcommonofwhichisnonsyndromiccleftlipand/orpalateCL/P,haveemergedasacomponentpartoftheWorldHealthOrganisation'sNonCommunicableDiseases(NCD)agenda;anditwasagreedatthe63rdWorldHealthAssemblyinMay2010thatduetotherisingtideofbirthdefects,theseshouldbeprioritisedinhealthpolicybymemberstatesaroundtheworld.ThishasledtotheinclusionofCL/PinthesubsequentGlobalBurdenofDisease(GBD)agendaandithasbecomeapparentthatintheabsenceofinterventionthereisaveryhighneo-natalmortalityassociatedwithcleftlipandpalateinthedevelopingworld.ThereisalsoconvincingevidencethatdeathanddisabilityduetocongenitalmalformationshasbeengrosslyunderrepresentedintheGBDhithertoandthisissuerequiresconcertedglobalattention.Global epidemiology:inconsensusmeetingsco-ordinatedbytheWHObetween2000and2004,effortstoco-ordinatethedescriptiveepidemiologyofCL/Paroundtheworldhasresultedinametaanalyticapproachco-ordinatedbytheInternationalClearingHouseforbirthdefects(ICBD)basedinRome,Italy.ThishascollectedinformationfromregistriesaroundtheworldinaformatthatallowsdatacomparisonandanestimateofglobalbirthprevalenceofCL/P;andalsoestablishesaninfrastructurethatfacilitatestheplanningofhealthservicestomeettheburdenimposedbyorofacialcleftcare.Global oral health inequalities research network (GOHIRN):TheIADRhaveestablishedanewoverarchingnetworkthatidentifiestheimportanceoforaldiseasesasamajorpublichealthissueandthatmajorinequalitiesinoralhealthexistbothwithinandbetweencountries.ThisgroupwillworkwithmajorinternationalstakeholderstoaddressissuessuchastheMillenniumDevelopmentGoalsandworktoaddressoralhealthinequalitiesusinga“commonriskfactor”approachalongsideothermajornon-communicablediseasessuchascardiovasculardisease,cancers,diabetes,obesityandrespiratorydisorders.Theobjectiveswillbetoinfluenceclinicians,educators,policymakers,researchersandresearchfundersaroundtheworld.European cleft research:forthelastdecadesignificantadvanceshavebeenmadearoundtheworldin(a)improvingtheevidencebaseforbesttreatmentprotocolsinthemanagementofinfantsbornwithCL/Pand(b)significantadvancesinknowledgeofgeneticandenvironmentalaetiology.AseriesofEuropeaninitiativesfromSCANDCleft,EUROCleft,theEuropeanScienceFoundation(ESF),EUROCRANandnowEUROCleftNethavemadeasignificantcontributionandpresentfutureopportunitiesintheco-ordinationofglobalresearcheffortsandaimtowardsestablishingstandardisedresearchprotocolswhichwillultimatelyallowinter-centrecomparisons.Genomics approach:Thispresentationwillprovidethecompellingevidenceforastronggeneticcomponentinnon-syndromicCL/Pandwilldescribethegeneticapproachesfortheidentificationofcausativegenes.Thiswillincludeselectedcandidategeneassociationstudies,linkagestudies,genomewideassociationstudies(GWAS),arraycomparativegenomichybridisation(CGH)andinformativeanimalmodels.UniqueinsightsintothemolecularpathogenesisofCL/Pthroughcandidategenepathwayswillincludeinterferonregulatoryfactor6(IRF6),ventralanteriorhomeobox1(VAX1)andtheMSX1andBMPsignallingpathways.Inthecontextofdeterminingthegeneticaetiologyofclefts,itisalsoimportanttoconsidertheimplicationsofheterogeneity,cleftsub-phenotypes,inter-populationdifferencesandgene/environmentinteractionandstrategiesforfuturestudiestoenhanceunderstandingofthemolecularpathogenesisofCL/Pthroughfunctionalgenomics,epigenetics,geneexpressionandconsideringanarrayofapproachestoidentifyrarermissensemutationsinthepathogenesisofcommon,complexdiseases.Theclinicalimplicationsofanimprovedcharacterisationofgeneticaetiologyintermsofpreventionwillbediscussed.

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Peter A. Mossey

CURRICULUM VITAE

Education

• BDS1983Dentistry,UniversityofDundee• PhDUniversityofGlasgow1994CraniofacialGenetics• FDS,RCSRoyalCollegeofSurgeonsofEdinburgh1987

Dentistry• DOrth,RCSRoyalCollegeofSurgeonsofEdinburgh1987

Orthodontics• MOrth,RCSRoyalCollegeofSurgeonsofEngland1988

Orthodontics• FFDRCSI,RoyalCollegeofSurgeonsinIreland,1988

Orthodontics• FDSRCPS,RoyalCollegeofPhysiciansandSurgeonsof

Glasgow,2005Dentistry• ILTM2001,MembershipoftheHigherEducationAcademyPosition

1983-1983 Associate GeneralDentalPractice Fermanagh,NorthernIreland1984-1984 HouseOfficerOrthodontics, DundeeDentalHospital Dundee,Scotland1984-1985 SeniorHouseOfficer OralSurgery,DundeeDentalHospital.(Resident) Dundee,Scotland1985-1987 Registrar,Orthodontics VictoriaHospital Kirkcaldy,Fife,Scotland1987-1989 Registrar,Orthodontics EdinburghDentalHospital Edinburgh,Scotland1989-1989 SeniorRegistrar(Locum), Orthodontics,RoyalVictoriaHospital Bournemouth1989-1994 Lecturer/Hon.SeniorRegistrarOrthodontics, GlasgowDentalHospitalandSchool Glasgow,Scotland1994–1997 LecturerinOrthodontics DundeeUniversityDentalSchool Dundee,Scotland1997–2000 SeniorLecturer DundeeUniversityDentalSchool Dundee,Scotland2000–2003 Reader DundeeUniversityDentalSchool Dundee,Scotland2003–present ProfessorofCraniofacialDevelopmentand DentofacialOrthopaedics DundeeUniversityDentalSchool Dundee,Scotland

Publications

Mossey,P.A.(1997)1.Chapter:“ClinicalskillsassessmentinDentistry”In“GuidetoAssessmentofStudentsProgressandAchievements”Editors:Godfrey,JandHeylings,D.PublicationproducedbytheMedicalandDentalEducationNetworkasaStudyGuideforcirculationtoallUKMedicalandDentalSchoolsinMarch1997.Mossey,P.A.(1997)2.Chapter:“StructuredClinicalOperativeTests”Acceptedforpublicationin“InnovationsinClinicalTeaching”Dennick,R.G.(Ed.)SEDAPublications,Birmingham,March1997.Mossey,P.A.andGilmour,M.(Eds)(1998)3.ReportofproceedingsofEuropeanScienceFoundationExploratoryconference,Dundee,September1997.

“Interactionofgenesandmaternalnutritioninorofacialclefting:aetiology,pathogenesisandexplorationofpreventivestrategies”.UniversityofDundee,DentalHealthServicesResearchUnit.ISBN1899809171.Mossey,P.A.andStirrups,D.R.Eds(1998)4.CorecompetenciesinDentistry:ExploringtheissuesReportofproceedingsofMADENmeetingandthefirstmeetinginUKtodiscussclinicalcompetenciesintheDentalcurriculumPublicationproducedbytheMedicalandDentalEducationNetwork(June1998)ISBN0953102513Mossey,P.A.,Newton,J.P.,Mason,A.andStirrups,D.R.5.Eds(1999)ClinicalcompetenciesinDentistry:“Assessingincompetence”(ReportofproceedingsofDecember1998MedicalandDentalEducationNetwork(MADEN)conference)PublicationproducedbyQueenMaryandWestfieldCollege(September1999)ISBN0953102548Ball,G.,McLennan,G.,McManners,J.,Mossey,P.A.,Raine,6.P.andReynolds,B.(1999)ScottishNeedsAssessmentProgramme(SNAP)documententitled“CleftLipandPalate”submittedtotheScottishOfficeinNovember1998.RecommendationscurrentlybeingimplementedintheManagedClinicalNetworkforOrofacialCleftsintheScottishNationalHealthService.SNAPReports,ScottishOffice,Nov.1998Mossey,P.A.,Trindade,I.E.K.,Shaw,W.C.,anddeSouza7.Freitas,J.A.Eds.(1999)InternationalTaskForceonCraniofacialAnomaliesConferenceReport“DevelopingstrategiesforcosteffectivetreatmentandpreventiveinterventionsforCleftLipandpalate”.ConferenceheldinBauru,SaoPaulo,Brazil,October2-5,1998.ISBNNo.85-87666-01-0Mossey,P.A.Ed.(1999)8.EuropeanScienceFoundation(ESF),2ndInternationalCollaborativeWorkshop,Strasbourg20th/21stFebruary,

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1999“Developmentofmethodstoinvestigatetheinteractionbetweennutritional,environmentalandgeneticfactorsinearlyhumandevelopment:demonstrationprojectinorofacialclefts”ConferenceReport,UniversityofDundee,2000.ISBN1899809194Mossey,P.A.Ed.(2000)9.EuropeanScienceFoundation3rdInternationalCollaborativeWorkshop,Dundee,19th-20thMay2000.Gene-environmentinteractioninearlyhumandevelopment:demonstrationprojectonorofacialclefts.ConferenceReport,UniversityofDundee,2001.ISBN1899809216Mossey,P.A.andLittle,J.(2002)10.Chapter12:“Epidemiologyoforalclefts:aninternationalperspective”.InWyszynskiDF(Ed)Cleftlipandpalate.Fromorigintotreatment.pp127-158.OxfordUniversityPress(August2002)ISBN:0-19-513906-2NOTE:Thisbookhaswonthe2003AAP/PSPaward11.forexcellenceinscholarlypublishingwithinclinicalmedicine.ThoseinitialsstandforAmericanAssociationofPublishers/ProfessionalandScholarlyPublishing.Authors/EdsMossey,P.A.,Munger,J.C.andShaw,W.C.12.Eds(2002)GlobalStrategiesTowardsReducingtheHealthCareBurdenofCraniofacialAnomaliesWHOReports,HumanGeneticsProgramme:ManagementofNoncommunicableDiseases:InternationalCollaborativeResearchonCraniofacialAnomalies,WHOpublications,Geneva,Switzerland.ISBN9241590386Authors/Eds:Mossey,P.A.andCastillia,E.(2003)13.GlobalRegistryandDatabaseonCraniofacialAnomaliesWHOReports,HumanGeneticsProgramme:InternationalCollaborativeResearchonCraniofacialAnomalies,WHOpublications,Geneva,Switzerland.ISBN9241591102Authors/Eds:Mossey,P.A.,Holsgrove,G.,Stirrups,D.R.,14.andDavenport,E.(2006)EssentialSkillsfortheNewDentist–OxfordUniversityPress(OUP)PublishedApril2006ISBN0-19-852619-9ChiefEditor:Mossey,P.A.(2006)15.AddressingtheglobalchallengesofcraniofacialanomaliesWHOReports,HumanGeneticsProgramme:ManagementofNoncommunicableDiseases:InternationalCollaborativeResearchonCraniofacialAnomalies,WHOpublications,Geneva,Switzerland.ISBN924159490XBearn,D.R.andMossey,P.A.(2011)16.Chapter3:“AetiologyandMalocclusion”.InOrthodontics,PrinciplesandPractice.Editors:Gill,D.S.,Naini,F.B.andDentalUpdate.Wiley-Blackwell,ISBN-13:978-1-4051-8747-3Mossey,P.A.,andModell,B.(2012)17.Chapter1:“EpidemiologyofOralClefts2012:AnInternationalPerspective”.In“CleftLipandPalate.Epidemiology,AetiologyandTreatment”EditorCobourne,M.T.FrontiersofOralBiology,Vol.16,p1-18.ISBN978-3-318-02107-3

Peter A. Mossey

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Clinical molecular diagnostics of congenital malformation syndrome using in-solution hybridization-based enrichment and massively parallel sequencing

Kenjiro Kosaki, M.D., Ph.D., F.A.C.M.G.

CenterforMedicalGenetics,KeioUniversitySchoolofMedicine

Ascataloguedingenetictextbookslike“Smith'sRecognizablePatternsofHumanMalformation”and“InbornErrorsofDevelopment”severalhundredsofgeneshavebeenshowntocausehumancongenitaldisorders.Theidentificationofthesecausativegeneshasofferedusawonderfulopportunitytodelineatethemolecularbasisofthesedisorders.Moleculardiagnosisoffersvaluableinformationtothepatientsandtheirfamiliesintermsofprognosis,preventingcomplications,andprovidingaccurategeneticcounseling.Theoretically,anygenecanbetestedbythedirectsequencingofPCRproductsamplifiedfromthepatient’sgenomicDNA.However,identifyingpathogenicmutationshasbeendifficultwhenthecausativegenehasalargenumberofexons.Insuchcases,directsequencingisexpensive,technicallydemanding,andtimeconsuming.Recently,nextgenerationsequencing[NGS]hasbeenintroduced.WearecurrentlydevelopingasensitiveandspecificmutationanalysissystemcoveringmostofthegenesenlistedintheSmith'stextbookwithtargetedenrichmentandmassivelyparallelsequencing.Inthissymposium,wewouldliketoshareourstrategieswiththeaudience.

Generallyspeaking,therearetwoNGSapproachesfordiagnosticsequencingingeneticdisorders:PCR-basedtargetedenrichmentfollowedbylong-readsequencingandin-solutionhybridization-basedenrichmentfollowedbyshort-readsequencing.In-solutionhybridization-basedenrichmentwasadoptedbecausePCRmethoddoesnotallowmultiplexenrichmentofthousandsofsequences.Aproof-of-principleexperimentwasperformedonthirtypatientswithneurofibromatosistypewasperformedandtheabilityofNGSprotocoltoidentifylikelydisease-causingmutationswasdemonstratedincomparisonwiththecurrentmethodology,Sangersequencing.Ourdiagnosticprotocolillustratesadrasticchangeintheclinicalmoleculardiagnosticsofcongenitalmalformationsyndromesandprovidesaparadigmforothergeneticconditions.

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Kenjiro Kosaki

CURRICULUM VITAE

Education

Undergraduate KeioUniversity,1985,TokyoJapanGraduate KeioUniversity,M.D.,1989,TokyoJapan KeioUniversity,DoctorofMedical Science(D.M.Sc.),1998,Tokyo,JapanLicensure Physician'slicenseinJapan,No.326408 ECFMGCertificate,No.0-434-038-6BoardCertification JapanPediatricSociety,1993 AmericanBoardofMedicalGenetics (M.D.ClinicalGenetics),1996Position

1989-1993 ResidentinPediatrics KeioUniversityHospital,TokyoJapan1993-1997 FellowinGenetics/Dysmorphology UniversityofCalifornia,SanDiego SanDiego,CA,USA1997-1998 FellowinDevelopmentalPathology BaylorCollegeofMedicine Houston,TX,USA1998-1999 InstructorofMedicalGenetics DepartmentofPediatrics KeioUniversitySchoolofMedicine Tokyo,Japan1999-2003 Chief,DivisionofMedicalGeneticsand Dysmorphology AssistantProfessorofPediatrics KeioUniversitySchoolofMedicine Tokyo,Japan2003-2011 Chief,DivisionofMedicalGeneticsand Dysmorphology AssociateProfessorofPediatrics KeioUniversitySchoolofMedicine Tokyo,Japan2012-Present Director,CenterforMedicalGenetics ProfessorofMedicalGenetics KeioUniversitySchoolofMedicine Tokyo,Japan

Award and Honors

1993 Japan-NorthAmericaMedicalExchange1994 Foundation FellowshipAward.1995 SanDiegoChildren'sHospitalResearchAward.1998 HowardHughesMedicalInstitute PostdoctoralResearchFellowshipforPhysicians

Publications

1. AsaiS,TanakaM,MiyakoshiK,KimSH,MinegishiK,MatsuzakiY,KosakiK,OgataH,YoshimuraY.AcaseofTessiernumber7cleftwithseveremicrognathia:prenatalsonographicandthree-dimensionalhelicalcomputedtomographicimages.PrenatalDiagnosis2010;30:159-161.

2. InoueH,TakadaH,KusudaT,GotoT,OchiaiM,KinjoT,MuneuchiJ,TakahataY,TakahashiN,MorioT,KosakiK,HaraT.SuccessfulcordbloodtransplantationforaCHARGEsyndromewithCHD7mutationshowingDiGeorgesequenceincludinghypoparathyroidism.EuropeanJournalofPediatrics2010;169:839-844.

3. KosakiR,KikuchiS,KoinumaG,HiguchiM,ToriiC,KawasakiK,KosakiK.TwopatientswithRubinstein-Taybisyndromeandseverepulmonaryinterstitialinvolvement.AmericanJournalofMedicalGenetics2010;152:1844-1846.

4. HosokawaS,TakahashiN,KitajimaH,NakayamaM,KosakiK,OkamotoN.AcaseofBrachmann-deLangesyndromewithcongenitaldiaphragmaticherniaandNIPBLgenemutation.CongenitalAnomalies2010;50:129-132.

5. YagihashiT,HatoriK,IshiiK,ToriiC,MomoshimaS,TakahashiT,KosakiK.Juvenilemuscularatrophyofaunilateralupperextremity(Hirayamadisease)inapatientwithCHARGEsyndrome.MolecularSyndromology2010;1:91-94.

6. OhnukiY,ToriiC,KosakiR,YagihashiT,SagoH,YasukawaK,TakahashiT,KosakiK.Cri-du-chatsyndromecytogeneticallycrypticrecombinationaneusomyofchromosome5:Implicationsinrecurrenceriskestimation.MolecularSyndromology2010;1:95-98.

7. IzumiK,TakagiM,ParikhA,HahnA,MiskovskyS,NishimuraG,ToriiC,KosakiK,HasegawaT,NeilsonDE.LatemanifestationsofTricho-Rhino-Pharangealsyndromeinapatient:Expandedskeletalphenotypeinadulthood.AmericanJournalofMedicalGenetics2010;152:2115-2119.

8. FukushimaH,KosakiK,SatoR,YagihashiT,GatayamaR,KodoK,HayashiT,NakazawaM,TsuchihashiT,MaedaJ,KojimaY,YamagishiH,TakahashiT.MechanismsunderlyingearlydevelopmentofpulmonaryvascularobstructivediseaseinDownsyndrome:AnimbalanceinbiosynthesisofthromboxaneA2andprostacyclin.AmericanJournalofMedicalGenetics2010;152:1919-1924.

9. MitsuhashiT,YonemotoJ,SoneH,KosugeY,KosakiK,TakahashiT.　Inuteroexposuretodioxincausesneocorticaldysgenesisthroughtheactionsofp27Kip1.ProceedingsoftheNationalAcademyofSciencesoftheUnitedStatesofAmerica2010;107:16331-16335.

10. SudaN,HattoriM,KosakiK,BanshodaniA,KozaiK,TanimotoK,MoriyamaK.Correlationbetweengenotypeandsupernumerarytoothformationincleidocranialdysplasia.OrthodonticsandCraniofacialResearch,2010;13:197-202.

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11.NarutoT,YokosukaT,TanoshimaR,KatoH,KajiwaraR,FujiiH,TanakaF,GotoH,YagihashiT,KosakiK,YokotaS.InfluenceofCYP3A5andABCB1genepolymorphismsoncalcineurininhibitor-relatedneurotoxicityafterstemcelltransplantation.ClinicalTransplantation2010;24:855-861.

12.YamadaK,FukushiD,OnoT,KondoY,KimuraR,NomuraN,KosakiK,YamadaY,MizunoS,WakamatsuN.Characterizationofadenovobalancedt(4;20)(q33;q12)translocationinapatientwithmentalretardation.AmericanJournalofMedicalGenetics2010;152:3057-3067.

13.HondaH,TakuboK,OdaH,KosakiK,TazakiT,YamasakN,MiyazakiK,MooreK,HondaZ,SudaY,LemischkaI.Hemp,anmbtdomain-containingprotein,playsessentialrolesinhematopoieticstemcellfunctionandskeletalformation.ProceedingsoftheNationalAcademyofSciencesoftheUnitedStatesofAmerica,2011;108:2468-2473.

14.KosakiK.Roleofrarecasesindecipheringthemechanismsofcongenitalanomalies:CHARGEsyndromeresearch.CongenitalAnomalies2011;51:12-15.

15.WatanabeK,OkadaE,KosakiK,TsujiK,IshiiT,NakamuraM,ChibaK,ToyamaY,MatsumotoM.SurgicaltreatmentforscoliosisinpatientswithShprintzen-GoldbergSyndrome.JournalofPediatricOrthopedics2011;31:186-193.

16.KosakiR,FujitaH,UeokaK,ToriiCKosakiK.Overgrowthofprenatalonsetassociatedwithsubmicroscopic9q22.3deletion.AmericanJournalofMedicalGenetics,2011;155:903-905.

17.KosakiR,FujitaH,TakadaH,OkadaM,ToriiC,KosakiK.MonozygotictwinsofRubinstein-TaybiSyndromediscordantforglaucoma.AmericanJournalofMedicalGenetics,2011;155:1189-1191.

18.KamoM,OhyamaM,KosakiK,AmagaiM,EbiharaT,NakayamaJ,IshikoA.Ichthyosisfollicularis,alopecia,andphotophobiasyndrome:acasereportandapathologicalinsightintopilosebaceousanomaly.AmericanJournalofDermatopathology.2011;33:403-406.

19.KosakiK,SaitoH,KosakiR,ToriiC,KishiK,TakahashiT.Branchialarchdefectsand19p13.12microdeletion:definingthecriticalregionintoa0.8Mbaseinterval.AmericanJournalofMedicalGenetics,2011;155:2212-2214.

20. SasakiK,OkamotoN,KosakiK,YorifujiT,ShimokawaO,MishimaH,YoshiuraKI,HaradaN.Maternaluniparentalisodisomyandheterodisomyonchromosome6encompassingaCUL7genemutationcausing3Msyndrome.ClinicalGenetics.2011;80:478-483.

21.YoshihashiH,OhkiH,ToriiC,IshikoA,KosakiK.SurvivalofamalemosaicforPORCNmutationwithmildfocaldermalhypoplasiaphenotype.PediatricDermatology.2011;28:550-554.

22.NumabeH,SawaiH,YamagataZ,MutoK,KosakiR,YukiK,KosakiK.Reproductivesuccessinpatientswith

Hallermann-Streiffsyndrome.AmericanJournalofMedicalGenetics,2011;155:2311-2313.

23.FryssiraH,MakrythanasisP,KattamisA,StokidisK,MentenB,KosakiK,WillemsP,KanavakisE.SevereDevelopmentalDelayinaPatientwith7p21.1-p14.3MicrodeletionSpanningtheTWISTGeneandtheHOXAGeneCluster.MolecularSyndromology.2011;2:45-49.

24.NishinaS,KosakiR,YagihashiT,AzumaN,OkamotoN,HatsukawaY,KurosawaK,YamaneT,MizunoS,TsuzukiK,KosakiK.OphthalmicfeaturesofCHARGEsyndromewithCHD7mutations.AmericanJournalofMedicalGenetics,2012;158:514-518.

25.TakenouchiT,NakazawaM,KanemuraY,ShimozatoS,YamasakiM,TakahashiT,KosakiK.HydrocephaluswithHirschsprungdisease:severeendofX-linkedhydrocephalusspectrum.AmericanJournalofMedicalGenetics,2012;158:812-815.

26.KosakiR,KanekoT,ToriiC,KosakiK.EECsyndrome-likephenotypeinapatientwithanIRF6mutation.AmericanJournalofMedicalGenetics,2012;158:1219-1220.

27.TanakaR,TakenouchiT,UchidaK,SatoT,FukushimaH,YoshihashiH,TakahashiT,TsubotaK,KosakiK.CongenitalcornealstaphylomaasacomplicationofKabukisyndrome.AmericanJournalofMedicalGenetics,2012;158:2000-2002.

28.YagihashiT,KosakiK,OkamotoN,MizunoS,KurosawaK,TakahashiT,SatoY,KosakiR.Age-dependentchangeinbehavioralfeatureinRubinstein-Taybisyndrome.CongenitalAnomalies.2012;52:82-86.

29.TakenouchiT,OkunoH,KosakiR,AriyasuD,ToriiC,MomoshimaS,HaradaN,YoshihashiH,TakahashiT,AwazuM,KosakiK.MicroduplicationofXq24andHartsfieldsyndromewithholoprosencephaly,ectrodactyly,andclefting.AmericanJournalofMedicalGenetics,2012;158:2537-2541.

30.TakenouchiT,EnomotoK,NishidaT,ToriiC,OkazakiT,TakahashiT,KosakiK.12q14Microdeletionsyndromeandshortstaturewithorwithoutrelativemacrocephaly.AmericanJournalofMedicalGenetics,2012;158:2542-2544..

31.TakenouchiT,YagihashiT,TsuchiyaH,ToriiC,HayashiK,KosakiR,SaitohS,TakahashiT,KosakiK.Tissue-limitedringchromosome18mosaicismasacauseofPitt-HopkinsSyndrome.AmericanJournalofMedicalGenetics,2012;158:2621-2623.

32.NomuraT,TakenouchiT,FukushimaH,ShimozatoS,KosakiK,TakahashiT.CatastrophicAutonomicCrisisWithCardiovascularCollapseinSpinalMuscularAtrophyWithRespiratoryDistressType1.JournalofChildNeurology,inpress

33.OsumiT,MiharuM,FuchimotoY,MoriokaH,KosakiK,ShimadaH.ThegermlineTP53mutationc.722C>Tpromotesboneandlivertumorigenesisatayoungage.PediatricBloodandCancer,inpress.

Kenjiro Kosaki

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13

The Osteocyte as a Regulator of Bone Remodeling

Lynda F. Bonewald, Ph.D.

UniversityofMissouri-KansasCity

Astheskeletonmatures,theratioofosteocytestootherbonecellssuchasosteoblastsand

osteoclastsincreasestoapproximately90-95%osteocytesintheadultskeleton.Theosteocyte

isaterminallydifferentiatedcelllocalizedwithinmineralizedmatrixtherebyunabletodivide

whilewithinthisenvironment.Osteocytescanremainviablefordecadesinthebonematrix.

Toremainviable,thesecellsareexposedtobonefluidwhichprovidesnutrientsbutalsoallows

theosteocytetosendmolecularmessagestoothercells.Osteocytesareconnectedtoeachother

andcellsonthebonesurfaceandthemarrowspaceviatheirdendriticprocessesrepresenting

anothermodeofosteocytecommunication.Themorphologyandotherpropertiesallowthis

celltobeexquisitelysensitivetomechanicalloadingandunloadingwhichistranslatedinto

signalssuchassclerostinorRANKLtoregulateosteoblasticboneformationandosteoclastic

boneresorption.Manyoftheeffectsofosteotropicfactorssuchasparathyroidhormoneare

mediatedthroughosteocytes.Therefore,theosteocyteisamajorregulatorofbonemodeling

andremodeling.Effectsofagingontheskeletonmaybethroughchangesintheosteocyte.

Maintainingoroptimizingosteocytefunctionmayabrogatebonelossandmaintainbonemass.

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Lynda F. Bonewald

CURRICULUM VITAE

Education

1973 B.A.(Biology)UniversityofTexas,Austin,TX,1984 Ph.D.(Immunology/Microbiology)MedicalUniversityof SouthCarolina,Charleston,SC.Position

1993-1998 AssociateProfessor,DepartmentofBiochemistry; UniversityofTexasHealthScienceCenter,San Antonio,Texas1992-1998 VAResearchInvestigator,AudieMurphy VeteransAdministration,MedicalCenterHospital, SanAntonio,TX1992-1998 AssociateProfessor,DepartmentofCellularand StructuralBiology,UniversityofTexasHealth ScienceCenter,SanAntonio,TX1992-1998 AssociateProfessorofMedicine,Department ofMedicine;UniversityofTexasHealthScience Center,SanAntonio,TX1998-2001 ProfessorofMedicine,DepartmentsofMedicine, Biochemistry,andCellularandStructuralBiology, UniversityofTexasHealthScienceCenter,San Antonio,TX2001-present LefkowitzProfessorofOralBiologyandDirector oftheBoneBiologyResearchProgram,Schoolof Dentistry,UniversityofMissouriatKansasCity, KansasCity,MO.2009-present Director,UMKCCenterofExcellenceinthe StudyofDentalandMusculoskeletalTissues2009-present UMKCViceChancellorforResearchand EconomicDevelopmentInterim

Award and Honors

1996-1999 CouncilMember,AmericanSocietyforBoneand MineralResearch1997-2001 ExecutiveBoard,AssociationofBiomolecular ResourceFacilities1998-2000 President,AssociationofBiomolecularResource Facilities1999-2004 NIHNIDCRBoardofScientificCounselors2001-2004 Chair,NIDCRBoardofScientificCounselors2001-2004 FASEBBoardofDirectors,non-voting2001-2004 Vice-Chair,NationalOsteoporosisFoundation, ScientificAdvisoryBoard2004-2005 InternationalOsteoporosisFoundation2005 UniversityofMissouriCurator’sProfessor2006 DistinguishedScientistAwardinMineralized TissueIADR/AADR2006 “RIB”Award,SunValleyWorkshop2011-present NIHNIAMSCouncil2011 President-elect,AmericanSocietyforBoneand MineralResearch

Publications

1. WangAC,ZhangHS,BonewaldL,TungE,BouvetJP,LiacoupoulusP:Structuralanalysisofamonotypickappachainwithincreasedmolecularweight.In:StreileinJW,AhmadF,BlackS,BlombergB,VoellmyRW(eds).CambridgeUniversityPress,NewYork,pp.335-336,1988.

2. MundyGR,BonewaldLF,RoodmanGD,ChenuC,OreffoROC,PfeilschifterJ,TGF βandBoneRemodeling.In:HImuraK.Shizume,S.Yoshida(eds).ProgressinEndocrinology1988.Vol2.ExcerptMedia,NewYork,927-931,1988.

3. MundyGR,BonewaldLF,Effectsofimmunecellproductsonbone.SorgC(ed)Macrophage-derivedcellregulatoryfactors.Cytokines.Basal,Karger,1989.1:38-53.

4. PfeilschifterJ,BonewaldL,MundyG:Theroleofgrowthfactorsincartilageandbonemetabolism.In:MSpornandABRoberts(eds):HandbookofExperimentalPharmacology:Peptidegrowthfactorsandtheirreceptors,Vol.95,SpringerVerlag,Heidelberg,Chapt.33,pp371-400,1990.

5. WoZ,BonewaldLF,OreffoROC,ChirgwinJ,CaponyF,RochefortH,MundyG.ThepotentialroleofprocathepsinDsecretedbybreastcancercellsinboneresorption.In:CohnDV,GlorieuxFH,MartinTJ(eds),CalciumRegulationandBoneMetabolism.Basicandclinicalaspects.Volume10,ExcerptaMedica,Amsterdam,pp.304-310,1990.

6. MundyGR,RoodmanGD,YonedaT,BonewaldL,OreffoR:Growthregulatoryfactorsinbonecellfunction.In:CalciumRegulationandBoneMetabolism.Basicandclinicalaspects.CohnDV,GlorieuxFH,MartinTJ(eds),Volume10,ExcerptaMedica,Amsterdam,pp.257-269,1990.

7. MundyGR,RoodmanGD,BonewaldLF,YonedaT,SabatiniM.EffectsofTNFandlymphotoxinonbonecells.In:AggarwalBBandVilickJ(eds),TumorNecrosisFactors:Structure,FunctionandmechanismsofAction.MarcelDekker,Inc.,NewYork,Chapt.21,pp483-498,1991.

8. MundyGR,RoodmanGD,BonewaldLF,OreffoROC,BoyceBF.Assaysforboneresorptionandboneformation.In:BarnesD,MatherJP,SatoGH(eds),MethodsinEnzymology:PeptideGrowthFactors,PartC,SectionVIII:TechniquesforStudyofGrowthFactorActivity.AcademicPress,Inc.,NewYork,Vol.198,Chapt.47,pp502-510,1991.

9. MundyGR,Bonewald,LF.TransformingGrowthFactorβ.In:CytokinesandBoneMetabolism.RussellRGandGowenM(eds).CRCPress,Inc.,Chapt.3,pp93-107,1992.

10.BonewaldLF.EffectsofEstrogenonGrowthFactorsinBone.In:ErnstScheringResearchFoundationWorkshop9SexSteroidsandBone.ZieglerR,PfeilschifterJ,BraütégramM(eds).Springer-Verlag,Chapt.5,pp71-94,1994.

11.FieldsGB,AngelettiRH,BonewaldLF,MooreWT,SmithAJ,StultsJT,WilliamsLC.Correlationofcleavagetechniqueswithside-reactionsfollowingsolid-phasepeptidesynthesis.In:TechniquesinProteinChemistryIV.Crabb,JW(ed),Chapt.IX,pp539-548,1995.

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12.HarrisSE,HarrisMA,FengJ,Ghosh-ChoudhuryN,DallasS,LaPointD,WozneyJ,BonewaldLF,MundyGR:Self-organizingbonecelldifferentiationinvitro:Asysteminsearchofthe"edgeofchaos".VthRecontresdeBlois"ChaosandComplexity",pp239-245,1995.

13.MundyGR,BoyceBF,YonedaT,BonewaldLF,RoodmanGD:Cytokinesandboneremodeling.Chapt.11,In:Osteoporosis,MarcusB,FeldmanD,KelseyJ(eds),AcademicPress,NewYork,pp301-313,1996.

14.AngelettiRH,BibbsL,BonewaldL,FieldsGB,McMurrayJS,MooreWT,StultsJT.Formationofadisulfidebondinanoctreotide-likepeptide:Amulticenterstudy.In:TechniquesinProteinChemistryVII.MarshakRR(ed),Chapt.V,pp261-274,1996.

15.BonewaldLF.TransforminggrowthfactorβIn:PrinciplesofBoneBiology.J.Bilezikian,L.Raisz,G.Rodan(eds),AcademicPressChapt46,pp647-660,1996.

16.FieldsGB,BibbsL,BonewaldLF,McMurrayJS,MooreWT,SmithAJ,StultsJT,WilliamsLC,andAngelettiRH.Multi-centerStudyofPost-assemblyProblemsinSolidPhasePeptideSynthesis.InPeptides:Chemistry,StructureandBiology.KaumayaPTP,HodgesRS(eds),MayflowerScientificLtd,pp52-54,1996.

17.AngelettiRH,BibbsL,BonewaldLF,FieldsGB,KellyJW,McMurrayJS,MooreWT,WeintraubST.Analysisofracemizationduring“standard”solidphasepeptidesynthesis:Amulticenterstudy.In:TechniquesinProteinChemistryVIII,D.MarshakRR(ed),AcademicPress,Chapter4,pp875-890,1997.

18.AngelettiRH,BonewaldLF,FieldsGB:SixYearStudyofPeptideSynthesisIn:MethodsInEnzymology.Vol.289pp607-717,1997.

19.BonewaldLF,DallasS.TheRoleofGrowthfactorsinboneformation.In:AdvancesinOrganBiology,MolecularandCellularBiologyofBone.E.E.BittarandM.Zaidi(ed),JAIPress,Inc.pp.591-614,1998.

20.BonewaldLF,AngelettiRH:AguidetoPeptideSynthesisandPeptideFacilitiesforBiomolecularResearchIn:ProfessionalSocieties,AssociationofBiomolecularResourceFacilities,byNieceRL,NaeveC.EncyclopediaofBioprocessTechnology,JohnWiley&Son.Vol.5,1-31,1999.

21.AmbulosNP,BibbsL,BonewaldLF,KatesSA,KhatriA,MedzihradskyKF,Weintraub,AnalysisofSyntheticPeptidesIn:Solid-PhasePeptideSynthesis:APracticalGuide.Eds.Albericio/Kates,MarcelDekker,Chapter19:751-789,2000.

22.BonewaldLF.Transforminggrowthfactor β .In:PrinciplesofBoneBiology.J.Bilezikian,L.Raisz,G.Rodan(eds),AcademicPress,Chapter49,Vol.2,903-918,2002.

23.BonewaldLF:QualityStandardsandComparativeSynthesesIn:MethodsofOrganicChemistry:SynthesisofPeptidesandPeptidomimetics,MurrayGoodman(ed),Houben-WeylChapter7.8,VolE22b,766-772,2003.

24.Bonewald,LF;CelltoCellandCell-MatrixInteractionsinBone.In:HandbookofCellSignalingVol3.R.Bradshaw(ed),AcademicPress,Chap.339,497-508,2003.

25.Bonewald,LF:Osteocytes.In:Osteoporosis,ThirdEdition.R.Marcus,D.Feldman,D.Nelson,C.Rosen(eds).ThirdEd.ElsevierInc.,Chap8,169-190,2007.

26.Klein-Nulend,J,Bonewald,LF:TheOsteocyte.In:PrinciplesofBoneBiology,ThirdEdition.J.Bilizikian,L.Raisz,TJMartin(eds).AcademicPress,Chap8,Vol.1.153-174,2008.

27.Dallas,SL,Alliston,A,Bonewald,LF:Transforminggrowthfactor β .In:PrinciplesofBoneBiology.J.Bilezikian,L.Raisz,TJMartin(eds),AcademicPress,Chapter53,Vol.2,1145-1166.2007.

28. LyndaF.Bonewald,CelltoCellandCell-MatrixInteractionsinBone.InRalphA.BradshawandEdwardA.Dennis,editors:HandbookofCellSignaling2ndedition,Oxford:AcademicPress,2009,pp.2647-2662.

29.Bonewald,LF:Osteocytes.In:PrimeronMetabolicBoneDisordersofMineralMetabolism.CliffordRosen,EdinChief,TheAmericanSocietyforBoneandMineralResearch,2025MStreet,N.W.,Suite800,Washington,DC20036-33097thEdition,Chapter4,22-26.2008.

30.Bonewald,LF,Dallas,SL,Gorski,JP“BoneMineralization”In:TheSkeletalSystem.OlivierPourquoi(ed),ColdSpringHarborLaboratoryPressChapter10,277-296,2009.

31.Bonewald,LF,Osteocytes.In‘FundamentalsofOsteoporosis’editedbyRobertMarcus,DavidFeldman,DorothyA.NelsonandCliffordJ.RosenAcademicPress,Chapter6,2009.

32.Bonewald,LF,“OsteocyteMechanosensationandTransduction”In:MechanosensingBiology.M.Noda(ed).Springer,Japan.2011.

33.Rosser,J,Bonewald,LF‘StudyingOsteocyteFunctionusingtheCellLinesMLO-Y4andMLO-A5’In:BoneResearchProtocols,SecondEdition.MiepHelfrichandStewardRalston,(eds).TheHumanaPress,Inc.SpringerProtocols,MethodsMolBiol.2012;816:67-81.PMID:22130923,2011.

34. Jaehn,K,Bonewald,LF.‘BoneCellBiology:Osteoblasts,Osteocytes,Osteoclasts’In:PediatricBone,SecondEdition.FrancisGlorieux,JohnPettifor,HaraldJueppner(eds).Elsevier,2011.

35. LyndaF.Bonewald,CelltoCellandCell-MatrixInteractionsinBone.InIntercellularSignalinginDevelopmentandDisease:EdwardA.DennisandRalphA.Bradshaw,editors:AcademicPress,2011,ISBN:9780123822154.

36. LYNDAF.BONEWALD,“CELLBIOLOGYOFCRANIOFACIALBone:Osteocytes”Chapter8,inMineralizedTissuesinOralandCraniofacialScience:BiologicalPrinciplesandClinicalCorrelatesEds:LaurieK.McCauleyandMarthaJ.Somerman,Wiley-Blackwell2012:63-70.

Lynda F. Bonewald

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New biological insights of tooth movement in response to mechanical stress

Keiji Moriyama, D.D.S., Ph.D.

SectionofMaxillofacialOrthognathics,TokyoMedicalandDentalUniversityGraduateSchoolTokyo,Japan

Orthodontictoothmovementisadynamicbiologicalphenomenon,whichistriggeredbythelossofequilibriuminthemechanicalenvironmentsurroundingthetoothuponorthodonticforceapplication.Todate,itiswidelyacceptedthatperiodontaltissue,includingcementum,periodontalligament(PDL)andalveolarbone,playindispensablerolesintoothmovementduetoitsuniquebiomechanical,cellular,andmolecularnatures,althoughthepreciseunderlyingmechanismsareyettobefullyelucidated.

Toinvestigatetheinvolvementofperiodontaltissueinmechanicalstress,wepreparedanexperimentaltoothmovementmodelinvivoanddemonstratedthattheforcedmechanicalstressstimulatedthetranscriptionofperiostin,whichisa90kDasecretedextracellularmatrix(ECM)implicatedincellularadhesionandmigration.Incontrast,occlusalhypofunctiondecreasestheexpressionofbothperiostinandtwist,abasichelix-loop-helixtranscriptionfactor,whichbindstoperiostinpromotertostimulateitstranscription.

Ontheotherhand,osteocytesarethoughttobethemajorbonecelltyperesponsibleforsensingmechanicalstrainandcoordinatingsignalsofboneresorptionandformation.Recentlyithasbeenreportedthattargeteddeletionofosteocytesbydiphtheria-toxin(DT)injectionintothemiceexpressingDTreceptorspecificallyinosteocytesresultsinboneloss,whereasthebonemassdoesnotdecreaseinresponsetounloadingexperimentbytailsuspensionofthesemice.Tofurtherelucidatetherolesofosteocytesinboneremodelingtriggeredbymechanicalloading/unloading,weconductedtoothmovementintheosteocyte-ablatedmiceandcomparedthedistanceoftoothmovementaswellasthehistologicalchangesbetweenthegroupswithorwithoutintraperitonealDTinjection.ThedistanceoftoothmovementinDT-injectedmicewassignificantlysmallerthanthatinDT-uninjectedmiceonday12.Interestingly,thenumberofTRAP-positiveosteoclastsdecreasedinDT-injectedmiceafterday8,comparedwiththatinDT-uninjectedmice.Theseresultssuggestthatosteocytesareinvolvedinosteoclastformationinresponsetothechangeofmechanicalenvironment,andthatosteocytesplayacrucialroleinmechanicalstress-inducedboneremodelingduringtoothmovement.

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Keiji Moriyama

CURRICULUM VITAE

Education

1980-1986 TokyoMedicalandDentalUniversity1986 D.D.S.(DoctorofDentalSurgery)1986-1990 TokyoMedicalandDentalUniversityGraduate School,2nd.DepartmentofOrthodontics1990 Ph.D.(DoctorofPhilosophy,TokyoMedicaland DentalUniversity)Position

1990-1992 Seniorresident,2ndDepartmentofOrthodontics, TokyoMedicalandDentalUniversity,Tokyo, Japan1992-1994 PostDoctoralFellow,DepartmentofMedicine, DivisionofEndocrinologyandMetabolism, UniversityofTexasHealthScienceCenteratSan Antonio,SanAntonioTexas,U.S.A.1994-1997 Instructor,2nd.DepartmentofOrthodontics, TokyoMedicalandDentalUniversity,Tokyo, Japan1997 JuniorAssociateProfessor,2ndDepartmentof Orthodontics,TokyoMedicalandDental University1998-2007 ProfessorandChairman,Departmentof OrthodonticsandDentofacialOrthopedics,The UniversityofTokushima2007–present ProfessorandChairman,Departmentof MaxillofacialOrthognathics,GraduateSchool, TokyoMedicalandDentalUniversity2011–present DirectorofDentalSchool,TokyoMedicaland DentalUniversity

Award and Honors

1993 YoungInvestigatorAward,FifteenthAnnualMeetingoftheAmericanSocietyforBoneandMineralResearch,Tampa,Florida

Publications

1. Izawa,T.,Ishimaru,N.,Moriyama,K.,Kohashi,M.,Arakaki,R.,Hayashi,Y.:CrosstalkbetweenRANKLandFassignalingindendriticcellscontrolsimmunetolerance.Blood110(1):242-250(2007)

2. OsakaN,TakahashiT,MurakamiS,MatsuzawaA,NoguchiT,FujiwaraT,AburataniH,Moriyama,K.,TakedaK,IchijoH.ASK1-dependentrecruitmentandactivationofmacrophagesinducehairgrowthinskinwounds.JCellBiol176(7):903-909(2007)

3. NishiM,YasueA,KinouchiN,NojiS,Moriyama,K..Theincreasesintheskeletalmusclemassofthetransgenicmiceexpressingthemutatedmyostatinaffectedcraniofacialmorphology.OrthodWaves.66(3):73-78,2007.

4. SudaN,HamadaT,HattoriM,ToriiC,KosakiK,Moriyama,K.DiversityofsupernumerarytoothformationinsiblingswithcleidocranialdysplasiahavingidenticalmutationinRUNX2-Possibleinvolvementofnon-geneticorepigeneticregulation.OrthodCraniofacRes.10:222-225,2007.

5. KinouchiN,OhsawaY,IshimaruN,OhuchiH,SunadaY,HayashiY,TanimotoY,Moriyama,K.,NojiS.Atelocollagen-mediatedlocalandsystemicapplicationsofmyostatin-targetingsiRNAincreaseskeletalmusclemass.GeneTher.15(15):1126-30,2008

6. Sato-WakabayashiM,Inoue-AraiMS,OnoT,HondaE,KurabayashiT,Moriyama,K.CombinedfMRIandMRImovieintheevaluationofarticulationinsubjectswithandwithoutcleftlipandpalate.CleftPalateCraniofacJ.45(3):309-14,2008

7. HashimotoK,OtsukaR,MinatoA,Sato-WakabayashiM,TakadaJ,Inoue-AraiMS,MiyamotoJJ,OnoT,OhyamaK,Moriyama,K.Short-termchangesintemporomandibularjointfunctioninsubjectswithcleftlipandpalatetreatedwithmaxillarydistractionosteogenesis.OrthodCraniofacRes.11(2):74-81,2008

8. GereltzulE,BabaY,SudaN,ShigaM,InoueM,TsujiM,ShinI,HirataY,OhyamaK,Moriyama,K.CaseReportofdenovoDup(18p)/Del(18q)andR(18)Mosaicism.JournalofHumanGenetics53(10):941-6,2008

9. OkudairaM,OnoT,KawamotoT,Moriyama,K.Three-dimensionalanalysisoflowerlipmovementduringarticulationinsubjectswithmandibularprognathism.OrthodWaves.67(3):93-103,2008

10.OkudairaM,KawamotoT,OnoT,Moriyama,K.Soft-tissuechangesinassociationwithanteriormaxillaryosteotomy:apilotstudy.OralMaxillofacSurg.12(3):131-8,2008

11.MiraouiH,OudinaK,PetiteH,TanimotoY,MoriyamaK,MariePJ.Fibroblastgrowthfactorreceptor2promotesosteogenicdifferentiationinmesenchymalcellsviaERK1/2andproteinkinaseCsignaling.JBiolChem.284(8):4897-904.2009

12. Inoue-AraiMS,OnoT,HondaE,KurabayashiT,MoriyamaK.Motorcoordinationofarticulatorsdependsontheplaceofarticulation.BehavBrainRes.199(2):307-16.2009

13.YagiY,SudaN,YamakoshiY,BabaO,MoriyamaK.Invivoapplicationofamelogeninsuppressesrootresorption.

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JDentRes.88(2):176-81.200914.HiasaM,AbeM,NakanoA,OdaA,AmouH,KidoS,

TakeuchiK,KagawaK,Yata,HashimotoT,OzakiS,AsaokaK,TanakaE,MoriyamaK,MatsumotoT.GM-CSFandIL-4inducedendriticcelldifferentiationanddisruptosteoclastogenesisthroughM-CSFreceptorsheddingbyup-regulationofTNF- αconvertingenzyme(TACE).Blood,114(20):4517-4526.2009.

15. InokuchiT,KawamotoT,AokiK,AokiA,NagahamaK,BabaY,SuzukiS,ShibayamaM,ManoY,OhyaK,MoriyamaK.Theeffectsofhyperbaricoxygenontoothmovementintotheregeneratedareaafterdistractionosteogenesis.CleftPalateCraniofacJ.47(4):382-392.2010

16.OnoT,OkumaM,HamadaT,MotohashiN,MoriyamaK.Acaseofringchromosome18syndrometreatedwithacombinedorthodontic-prosthodonticapproach.CleftPalateCraniofacJ.7(2):201-210.2010

17.AokiA,MoriyamaK,KawamotoT,AokiK,InokuchiT,KudohA,NagahamaK,BabaY,SuzukiS,OhyaK.Amountofbonelengtheningaffectsbloodflowrecoveryandbonemineralizationafterdistractionosteogenesisinacaninecleftpalatemodel.CleftPalateCraniofacJ.47(3):303-3132010.

18.KusumahSW,SuzukiS,ItohK,HigashinoR,OhbayashiN,KurabayashiT,MoriyamaK.MorphologicalobservationofthemedialpterygoidmusclebythesuperimpositionofimagesobtainedbylateralcephalogramandMRI.JOrthod.36(4):243-52,2009.

19.KondoY,TakahashiT,ObaY,TanakaE,MoriyamaK.Bloodflowdistributionofrepairedlipincleftlippatients.AngleOrthodont.79(6):1182-7,2009.

20.HattoriM,ToriiC,YagihashiT,IzumiK,SudaN,OhyamaK,TakahashiT,MoriyamaK,KosakiK.DiagnosisofRussell-Silversyndromebythecombinedbisulfiterestrictionanalysis-denaturinghigh-performanceliquidchromatographyassay.GenetTestMolBiomarkers.13(5):623-30,2009.

21. JinnoK,TakahashiT,TsuchidaK,TanakaE,MoriyamaK.AccelerationofpalatalwoundhealinginSmad3-deficientmice.J.Dent.Res.88(8):757-61,2009.

22.KitaseY,YokozekiM,FujiharaS,IzawaT,KurodaS,TanimotoK,MoriyamaK,TanakaE.Analysisofgeneexpressionprofilesinhumanperiodontalligamentcellsunderhypoxia:theprotectiveeffectofCCchemokineligand2tooxygenshortage.ArchOralBiol.54(7):618-24,2009.

23.MinatoA,OnoT,MiyamotoJJ,HondaE,KurabayashiT,MoriyamaK.Preferredchewingside-dependenttwo-pointdiscriminationandcorticalactivationpatternoftactiletonguesensation.BehavBrainRes.203(1):118-26,2009.

24. SudaN,ShigaM,GanburgedG,MoriyamaK.Marfansyndromeanditsdisorderinperiodontaltissues.JExpZoologBMolDevEvol.312B(5):503-9,2009.

25. SudaN,KawafujiK,MoriyamaK.Multidisciplinarymanagementincludingendodontics,periodontics,orthodontics,anteriormaxillaryosteotomyandprostheticsinanadultcasewithasevereopenbite.OrthodWaves,68(1),42-49,2009.

26. IshizakiT,BabaY,SuzukiS,DoiH,YoneyamaT,MoriyamaK.ComparisonoftheefficiencyoftwotypesofintraoralsplintsintheREDsystemformaxillarydistractionosteogenesis.OrthodWaves69(3):102-9,2010.

27. SudaN,HattoriM,KosakiK,BanshodaniA,KozaiK,TanimotoK,MoriyamaK.Correlationbetweengenotypeandsupernumerarytoothformationincleidocranialdysplasia.OrthodCraniofacRes.13(4):197-202,2010.

28.GanburgedG,SudaN,SaitoM,YamazakiY,IsokawaK,MoriyamaK.Dilatedcapillaries,disorganizedcollagenfibersanddifferentialgeneexpressioninperiodontalligamentsofhypomorphicfibrillin-1mice.CellTissueRes.341(3):381-95,2010.

29.TamuraR,OnoT,SatoM,HasegawaM,MoriyamaK,ArakiK.Associationbetweenpositionalchangesinlaboratoryvaluesandseverityinsubjectswithobstructivesleepapneasyndrome.JMedDentSci.57(2):147-54,2010.

30. SudaN,BazarA,BoldO,JigjidB,GaridkhuuA,GanburgedG,MoriyamaK.AMongolianpatientwithhypohidroticectodermaldysplasiawithanovelP121SvariantinEDARADD.OrthodCraniofacRes.13(2):114-7,2010.

31. InokuchiT,KawamotoT,AokiK,AokiA,NagahamaK,BabaY,SuzukiS,ShibayamaM,ManoY,OhyaK,MoriyamaK.Theeffectsofhyperbaricoxygenontoothmovementintotheregeneratedareaafterdistractionosteogenesis.CleftPalateCraniofacJ.47(4):382-92,2010.

32.AokiA,KawamotoT,AokiK,InokuchiT,KudohA,NagahamaK,BabaY,SuzukiS,OhyaK,MoriyamaK.Amountofbonelengtheningaffectsbloodflowrecoveryandbonemineralizationafterdistractionosteogenesisinacaninecleftpalatemodel.CleftPalateCraniofacJ.47(3):303-13,2010.

33.OnoT,OkumaM,HamadaT,MotohashiN,MoriyamaK.Acaseofringchromosome18syndrometreatedwithacombinedorthodontic-prosthodonticapproach.CleftPalateCraniofacJ.47(2):201-10,2010.

34.KawafujiA,SudaN,IchikawaN,KakaraS,SuzukiT,BabaY,OgawaT,TsujiM,MoriyamaK.SystemicandmaxillofacialcharacteristicsofpatientswithBeckwith-Wiedemannsyndromenottreatedwithglossectomy.AmJOrthodDentofacialOrthop.139(4):517-525.2011.

35.QiuL,HaruyamaN,SuzukiS,YamadaD,ObayashiN,KurabayashiT,MoriyamaK.Accuracyoforthodonticminiscrewimplantationguidedbystereolithographicsurgicalstentbasedoncone-beamCT-derived3Dimages.AngleOrthod.2011(inpress)

36.KurodaS,WatanabeK,IshimotoK,NakanishiH,MoriyamaK,TanakaE.Long-termstabilityofLeFortIIIdistractionosteogenesiswitharigidexternaldistractiondeviceinapatientwithCrouzonsyndrome.AmJOrthodDentofacialOrthop.2011(inpress)

37. SuzukiH,SudaN,ShigaM,KobayashiY,NakamuraM,IsekiS,MoriyamaK.ApertsyndromemutantFGFR2anditssolubleformreciprocallyalterosteogenesisofprimarycalvarialosteoblasts.JCellPhysiol.2011(inpress)

Keiji Moriyama

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Mechanisms of tooth renewal

Irma Thesleff, D.D.S., Ph.D.

InstituteofBiotechnology,UniversityofHelsinki,Finland

Thecapacityfortoothrenewalisquitelimitedinmammals.Themajormechanismoftoothrenewalinvertebratesistoothreplacementandinfishandreptilesteethcanbereplacedcontinuously.However,inmammalsthedeciduousdentition,orpartofit,canbereplacedbyasecondsetoffunctionalteeth,andthereismaximallyoneroundoftoothreplacement.Themechanismsoftoothreplacementhaveremainedlargelyunknownmainlybecausemicedonotreplacetheirteeth.Wehaveusedtheferretasamodelanimalandperformedmorphologicalandmolecularanalysesoftoothreplacement.Thereplacementteethareformedsuccessionallyfromtheirdeciduouspredecessors.Theydevelopfromthesocalleddentallaminaassociatedwiththeouterenamelepitheliumoftheprecedingtooth.Wehaverecentlylocalizedputativestem/progenitorcellsinthedentallaminaepitheliumduringtoothreplacement.Theseobservationshavealsoindicatedthattheremaybeacapacityforcontinuedtoothreplacementinmammals.

Inadditiontoreplacement,somemammalianteethcanberenewedbycontinuousgrowthwhichcompensatesfortoothwear.Wehaveexaminedthemechanismsofthecontinuousgrowthofthemouseincisor.Ourresultstogetherwithworkfromotherlaboratorieshaveindicatedthatthereisastemcellnicheintheproximalendoftheincisorinthesocalledlabialcervicalloop.ThemaintenanceanddifferentiationoftheepithelialstemandprogenitorcellsisregulatedbyacomplexnetworkofstimulatoryandinhibitorymoleculesaffectingFgf,Tgfbeta,Bmp,WntandHhsignalpathways.Thestemcellsresponsiblefortoothrenewalhavebeenidentifiedinthecervicalloop.WehaverecentlydemonstratedthatthesecellsexpressthestemcellmarkerSox2andthattheSox2positivecellscontributetoallepithelialcelllineagesoftheincisor.Takentogether,thecurrentdataindicatethattoothrenewalisbasedonepithelialstemandprogenitorcellswhichseemtohaveaconservedcommongeneticsignatureindifferenttypesoftoothrenewal,andthattheirmaintenanceanddifferentiationisregulatedbyanetworkofsameconservedsignalpathwaysthatregulatestoothmorphogenesis.

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Irma Thesleff

CURRICULUM VITAE

Education

1972 GraduationfromDentalSchool(DDS),Medical FacultyUniversityofHelsinki1975 DoctorofOdontology(Dr.Odont,PhD)University ofHelsinki1978-1979 VisitingAssociate(postdoc),Laboratoryof DevelopmentalBiologyandAnomalies, NIDR,Bethesda,MD,USA1980Docent(Lecturer) inDevelopmentalBiologyUniversityofHelsinki1983 Specialist'srightsinorthodonticsFinlandPosition

1973-1976 ResearchAssociate,theAcademyofFinland1976-1978 Instructor,Dept.ofPedodonticsandOrthodontics, UniversityofHelsinki1979-1983 Instructor,Dept.PedodonticsandOrthodontics, Univ.Helsinki1983-1990 Scientist,AcademyofFinland1990-2004 ProfessorandChairman,Departmentof PedodonticsandOrthodontics, UniversityofHelsinki

Award and Honors

1987 PohjolaPrize,FinnishDentalSocietyandFinnish DentalAssociation1993 DistinguishedScientistAwardinCraniofacial Biology,Int.Assoc.Dent.Res.(IADR)1994 FinnishAcademyofScienceandLetters(Suom. Tiedeakat.),invitedmember1995 Thuréusprize,Umeåuniversity1997 CityofHelsinkiScienceAward1997 HonoraryDoctorinOdontology,Universityof Göteborg1997 InternationalPrize,SwedishDentalSociety1998-2003 AcademyProfessor,AcademyofFinland1999 AndersJahrePrizeinMedicine,OsloUniversity2000 ActaOdontologicaScandinavicaPrizefor” Excellentcontributiontodentalresearch”2000 EMBO,invitedmember2002 HonoraryDoctorinOdontology,Universityof Copenhagen2004 HonoraryDoctorinScience,McGillUniversity, Montreal2005 ProfessoroftheYear,FinnishAssociationof UniversityProfessors2005 SheldonFrielMemorialLecturer,European OrthodonticSociety2005 FinnishSocietyofSciencesandLetters(Suom. Tiedeseura),invitedmember2005 HonoraryDoctor,KatholiekeUniversiteitLeuven, Belgium

2005-2010 HonoraryProfessorinCraniofacialandDental Genetics,UniversityofCopenhagen2006 WilliamJ.GiesAwardforbestpaperinJ.Dent.Res., IADR/AADR2008 Chair,GordonConferenceon“Craniofacial Morphogenesis&TissueRegeneration2008-2009 President,EuropeanOrthodonticSociety2008 HonoraryDoctor,UniversityofDebrecen,Hungary2008 IsaacSchourMemorialAward,IADR2008 HonoraryDoctor,UniversityofOslo2009 AAASFellow2009 ValkhofChair(VisitingProfessor),Radboud UniversityNijmegen,TheNetherlands2009 ApolloniaPrize,FinnishDentalSociety2010 PaulGoldhaberAward,HarvardSchoolofDental Medicine2010 HonoraryDoctor,KarolinskaInstitutet,Stockholm2011 ProfessorEJNyströmAward,FinnishSocietyof SciencesandLetters

Publications

199originalarticlesinpeerreviewedjournals105reviewarticlesandbookchaptershindex:71

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Role of dental epithelium- stem cell interactions during dental cell differentiation

Satoshi Fukumoto, D.D.S., Ph.D.

DivisionofPediatricDentistry,TohokuUniversityGraduateSchoolofDentistry

Toothmorphogenesisischaracterizedbyreciprocalinteractionsbetweenthedentalepitheliumandmesenchymalcellsderivedfromthecranialneuralcrest,whichresultintheformationofthepropernumberandshapesofteeth.Multipleextracellularsignalingmolecules,includingBMPs,FGFs,WNTs,andShh,havebeenimplicatedintheseinteractionsfortoothdevelopment.Theepithelialcellsthensubsequentlygiverisetoenamel-formingameloblasts,whilethedentalpulpstemcells(DPSCs)formdentin-formingodontoblastsanddentalpulpcells.Epithelial-mesenchymalinteractionsregulatethegrowthandmorphogenesisofectodermalorganssuchasteeth.TheinteractionsbetweenDPSCsandtheepitheliumhavenotyetbeenclearlyelucidated.Dentalpulpstemcellline(SP)thatwascomprisedofenrichedsidepopulationcellsandthatdisplayedamultipotentcapacitytodifferentiateintoodontogenic,osteogenic,adipogenic,andneurogeniccells.WethenanalyzedinteractionsbetweenSPcellsandcellsfromtheratdentalepithelialcellline(SF2).SPcellsdifferentiatedintoodontoblaststhatexpresseddentinsialophosphoproteinwhenculturedwithSF2cells.ThisdifferentiationwasregulatedbyBMP-2and-4andwasinhibitedbytheBMPantagonistNoggin.

Stemcellresearchhasidentifiedandestablishedseveraltypesofstemcells,includinginducedpluripotentstem(iPS)cells,whicharegeneratedfromavarietyofsomaticcelltypesviaintroductionoftranscriptionfactorsthatmediatepluripotencyandhasgreatpotentialfortissue-specificregenerativetherapies.Further,ameloblastssecreteenamel-specificextracellularmatrices,includingameloblastin(AMBN),andthesearelostupontootheruptionfollowingtransformationandapoptosis.Thismakesitimpossibletorepairorreplacedamagedenamelinaneruptedtooth.Sinceameloblastsarelostupontootheruption,identifyingalternativesourcesofthesecellsbecomesimportant.Sincedentalepithelialcells,whichdifferentiateintoenamelsecretingameloblasts,disappearinadultsaftertoothdevelopment,ourstrategytocreateameloblastsfrommouseiPScellsmayhavedirectapplicationinregenerativetoothmedicine.WefoundthatmouseiPScellsculturedwithmitomycin-CtreatedSF2cellsdisplayedanepithelialcell-likemorphology.Thesecellsexpressedtheepithelialcellmarkersp63andcytokeratin-14,andtheameloblastmarkersAMBN,butdidnotexpresstheendodermalcellmarkerGata6orthemesodermalcellmarkerbrachyury.ThisisthefirstdemonstrationofdifferentiationofiPScellsintoameloblaststhroughinteractionswiththedentalepithelium.

AnumberoffactorsarethoughttogiveiPScellsthecapacityfordirectorindirectdifferentiationintoameloblasts.Possibledirecteffectorsincludegapjunctions,intercellularbindingmolecules,adhesionfactorsandextracellularmatricessecretedbydentalepithelium.Growthfactorsmightalsobeinvolved,becauseconditionedmediumfromSF2cellsinducedAMBNexpressioniniPScells.AMBNisalsoacandidatefactorfordentalcelldifferentiationofiPScells,asSF2cellsexpressinglowlevelsofAMBNdidnotinducethedifferentiationofiPScells.AMBNhasdiversefunctionsinvariouscellularphysiologies,suchascellgrowth,differentiation,cellpolarizationandattachment,althoughthedetailedmechanismsofAMBNsignalingrequireadditionalinvestigation.AMBN-nullmicedisplaysevereenamelhypoplasiaduetoimpaireddentalepithelialcellproliferation,polarizationanddifferentiationintoameloblasts,aswellaslossofcellattachmentactivitywithimmatureenamelmatrix.TheseresultssuggestthatAMBNisnecessaryforbothinvivoandinvitroameloblastdifferentiation.

Co-culturingwithdentalepithelialcellsappearstoinducestemcelldifferentiationthatfavorsanodontogeniccellfateandthismightbeausefulapproachintoothbioengineering.

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Satoshi Fukumoto

CURRICULUM VITAE

Education

1988 GraduatedfromKurashiki-AmakiHighSchool (Okayama)1994 D.D.S.NagasakiUniversitySchoolofDentistry2000 Ph.D.(Dr.ofDentalScience)NagasakiUniversitySchool ofDentistryPosition

1994-1997 Instructor,NagasakiUniversitySchoolof Dentistry(DepartmentofPediatricDentistry)1997-2000. ResearchfellowoftheJapaneseSocietyforthe PromotionofScience2000–2003 Instructor,NagasakiUniversitySchoolof Dentistry(DepartmentofPediatricDentistry)2000-2002 VisitingFellow,MolecularBiologySection, CraniofacialDevelopmentalBiologyand RegenerationBranch,NationalInstituteofDental andCraniofacialResearch(NIDCR),National InstituteofHealth(NIH)(Chief.Yoshihiko Yamada)2003-2004 Assistantprofessor,NagasakiUniversitySchool ofDentistry(DepartmentofPediatricDentistry)2004-2007 Associateprofessor,KyushuUniversity,Faculty ofDentalScience(SectionofPediatricDentistry)2007- Professor,TohokuUniversityGraduateSchoolof Dentistry(DivisionofPediatricDentistry)

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Tooth Regenerative Therapy as a Future Dental Treatment

Takashi Tsuji, Ph.D.

GraduateSchoolofInnovationStudies(IntellectualPropertyManagement),TokyoUniversityofScience

Oralfunctionssuchasenunciation,masticationandocclusion,areanimportantaspectofgoodhealthandqualityoflife.Theseoralfunctionsareachievedinharmonywiththeteeth,masticatorymusclesandthetemporomandibularjointunderthecontrolofthecentralnervoussystem.Damage,lossandtheonsetofdiseaseinteeth,includingdentalcariesandperiodontaldisease,thuscausefundamentalproblemsfororalfunctionsandassociatehealthissues.Varioustherapiesforthesedentaldisordershavebeenestablishedusingartificialmaterialssuchasrootcanaltreatmentsandprosthesisprocedures.Furthermore,afterthelossofatooth,thetoothfunctionsaretraditionallyrestoredbyreplacementwithanartificialtooth,theuseofabridge,andalsoosseo-integrateddentalimplants.

Torestorethepartiallossoforganfunctionsandtorepairdamagedtissues,anattractiveconceptinregenerativetherapyisstemcelltransplantationintovarioustissuesandorgans.Dentaltissue-stemcellshavebeenidentifiedandwillhaveutilityforthedevelopmentofstemcelltransplantationtherapytorestorethepartiallossoforganfunctionandtherebyachievedentaltissuerepairsuchascariesandperiodontaldiseases.Theultimategoalofregenerativetherapyistodevelopfullyfunctioningbioengineeredorgansthatcanreplacelostordamagedorgansfollowingdisease,injuryoraging.Forthesuccessoftoothreplacementregenerativetherapy,abioengineeredtoothmustbecapableoferuptinginthelosttoothregioninanadultoralenvironmentandachievefullfunctionality,includingsufficientmasticatoryperformance,biochemicalcooperationwiththeperiodontaltissuesandproperresponsivenesstonoxiousstimulationsvianeuronsinthemaxillofacialregion.

Togeneratewholetooth,theapproachistorecreateorganogenesisthroughtheepithelial-mesenchymalinteractionsthatoccurinthedevelopingembryoandtherebydevelopfullyfunctioningbioengineeredorgansfromtheresultingbioengineeredorgangermgeneratedviathree-dimensionalcellmanipulationusingimmaturestemcellsinvitro.Wepreviouslydevelopedabioengineeringmethodforformingathree-dimensionalorgangermintheearlydevelopmentalstages,termedthe‘bioengineeredorgangermmethod’(NatureMethods4,227-230,2007).Thismethodwasadoptabletogeneratevariousorgangermssuchastooth,hairfollicles(NatureCommun.3,784,2012,Sci.Rep.2,424,2012),salivaryglandandlacrimalgland.Recently,wereportedfullyfunctioningbioengineeredtoothreplacementsafterthetransplantationsofabioengineeredtoothgerm(PNAS106,13475-13480,2009)ormaturetoothunitcomprisingthebioengineeredtoothandperiodontaltissuessuchasperiodontalligamentandalveolarbone(PLoSONE,6,e21531,2011)intoalosttoothregion.Thebioengineeredmolartoothgermcoulderuptandreachocclusionwithanopposingtoothaftertransplantationinthemouseadultoralenvironment.Thebioengineeredtoothunit,whichwascontrolledforlengthandshape,wassuccessfullytransplantedintoaproperly-sizedbonyholeinthealveolarbonethroughboneintegrationbyrecipientboneremodeling.Thesebioengineeredteethdisplayedphysiologicaltoothfunctionssuchasmastication,periodontalligamentfunctionforboneremodelingandresponsivenesstonoxiousstimulations.Toothregenerativetherapyhasthepotentialtoprovideessentialfunctionalrecoveryandultimatelyreplacethecurrentartificialmaterialsusedindentaltreatments.

Inthispresentation,Iwouldliketotalkanddiscussaboutthestrategiesandrecentprogressoftheresearchanddevelopmentfortheestablishmentoftoothregenerativetherapies.

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Takashi Tsuji

CURRICULUM VITAE

Education

1984 BSc,FacultyofScience,NiigataUniversity,Japan1986 MSc,GraduateSchoolofScience,Niigata University,Japan1989-1992 GraduateSchoolofScience,KyushuUniversity, Japan1993 PhD,GraduateSchoolofScience,Niigata University,JapanPosition

1986-1989 Researchers,CentralResearchLaboratories, YamanouchiPharmaceuticalCoLtd.1993-2000 SeniorResearcher,PharmaceuticalFrontier ResearchLaboratory,JTInc.2000-2007 AssociateProfessor,FacultyofIndustrialScience andTechnology,TokyoUniversityofScience2008 VisitingProfessor,LouisPasteurUniversity, French2007-Present Professor,GraduateSchoolofIndustrialScience andTechnology,TokyoUniversityofScience2009-Present Professor,ResearchInstituteofScienceand Technology,TokyoUniversityofScience2009-Present VisitingProfessor,TokyoDentalCollege,Japan2010-Present Professor,GraduateSchoolofInnovationStudies (IntellectualPropertyManagement), TokyoUniversityofScience

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Amelogenins: Multifaceted enamel matrix proteins in hard tissue biology

Naoto Haruyama, D.D.S., Ph.D.

GCOEProgram,InternationalResearchCenterforMolecularScienceinToothandBoneDiseases,TokyoMedicalandDentalUniversity

Amelogeninsarethemostabundantextracellularmatrixproteinssecretedbyameloblastsduringtoothdevelopmentandareimportantforenamelformation.Recently,amelogeninshavebeendetectednotonlyinameloblasts,whicharedifferentiatedfromtheepithelialcelllineage,butalsoinothertissues,includingmesenchymaltissuesatlowlevels,suggestingthatamelogeninspossessotherfunctionsinthesetissues.Inthefirstpartofthispresentation,theemergingevidencesfortheadditionalrolesoffull-lengthamelogenin(M180)andleucine-richamelogeninpeptide(LRAP)inmesenchymalcells,suchaschondrocytesandosteoblasts,willbeintroduced.Experimentsutilizingachondrogeniccellline,ATDC5,revealedthatthesupplementofrecombinantmouseM180-orLRAP-proteinintochondrogenesis-stimulatingmediumincreasedalkalinephosphatase(ALP)activityandglycosaminoglycansecretionat14and21daysofculture,respectively,ascomparedwiththecontrol.QuantitativePCR(Q-PCR)analysisindicatedthatLRAPincreasedthegeneexpressionlevelsofRunx2,Col2a1,andAggrecanat7daysofdifferentiation.Moreover,bothM180andLRAPsignificantlyincreasedthegeneexpressionlevelsofALP,Aggrecan,Col10a1,andOsteopontinat28daysofculture.BrdUassayandQ-PCRanalysisforWntsignallingindicatedthatbothM180andLRAPreducedthecellproliferation,butinducedthecelldifferentiationpossiblythroughalterednon-canonicalWntsignalling.Interestingly,amelogeninnullmiceshowedincreasedosteoclastogenesisandrootresorptioninperiodontaltissues.Recombinantamelogeninproteinssuppressosteoclastogenesisinvivoandinvitro,suggestingthatamelogenin,especiallyLRAP,wasinvolvedinpreventingidiopathicrootresorptionbyregulatingosteoclastogenesis(odontoclastogenesis).ToidentifyextendedfunctionsofLRAPinboneformationandresorption,wethenengineeredtransgenic(TgLRAP)miceusingamurine2.3kbα 1(I)-collagenpromotertodriveexpressionofLRAP.AlthoughLRAPexpressiondidnotaffectbonestructureinthesemice,theovariectomized(OVX)TgLRAPmiceresistedbonelossinducedbyovariectomyresultinginhigherbonemineraldensitycomparedtoOVXwildtype(WT)mice.ThequantitativeanalysisofcalceinintakesindicatedthattheOVXTgLRAPmicehadincreasedboneformationcomparedtoshamoperatedWTmice.TheparametersforboneresorptionintissuesectionsshowedincreasednumberofosteoclastsinOVXWT,butnotinOVXTgLRAPcomparedtoshamoperatedWTorTgLRAPmice.invitrocalvarialcellculturesisolatedfromtheTgLRAPmiceshowedincreasedALPactivityandincreasedformationofmineralizationnodules.TheTgLRAPcalvarialcellsalsoshowedinhibitoryeffectsonosteoclastogenesisinvitro.GeneexpressioncomparisonbyQ-PCRincalvarialcellsindicatedthatboneformationmakerssuchasRunx2,ALPandOsteocalcinwereincreasedinTgLRAP,comparedtoWTcells.Meanwhile,RanklexpressionwasdecreasedinTgLRAPcellsinvitro,supportingthebonephenotypesinOVXmice.TheseresultssuggestthattheLRAPhavedistinctrolestomaintainthebonemetabolism.Althoughamelogeninsareimplicatedintissue-specificepithelial-mesenchymalormesenchymal-mesenchymalsignaling,theprecisemolecularmechanismhasnotbeencharacterized.Toobtainaclueforthemechanism,theresultsofayeasttwo-hybridassayaimedatidentifyingprotein-bindingpartnersforLRAPwillbeintroducedinthelastpartofthispresentation.Thetherapeuticapplicationofanenamelmatrixderivative(EMDOGAIN®)richinamelogeninsresultedintheregenerationofcementum,alveolarbone,andperiodontalligamentinthetreatmentofexperimentalorhumanperiodontitis,indicatingtheattractivepotentialofamelogenininhardtissueformation.Gainingfurtherinsightsintothecellfunctionsmodulatedbythemultifunctionalamelogeninproteinswillleadtothedevelopmentofnewtherapeuticapproachesfortreatingdentaldiseasesanddisorders.

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Naoto Haruyama

CURRICULUM VITAE

Education

1992-1998 D.D.S.,TohokuUniversity,SchoolofDentistry, Sendai,Miyagi,Japan PassedtheExaminationofNationalBoard(1998)1998-2002 Ph.D.,TohokuUniversityGraduateSchoolof Dentistry,Sendai,Miyagi,Japan Major:OrthodonticsPosition

2002-2002 ClinicaldoctorinTohokuUniversityHospital (Orthodontics)2002-2003 AssistantprofessorinTohokuUniversity, GraduateSchoolofDentistry(Divisionof OrthodonticsandDentofacialOrthopedics)2003-2009 AssistantprofessorinTohokuUniversity, GraduateSchoolofDentistry (DivisionofOralDysfunctionScience)2004-2007 Visitingfellow,FunctionalGenomicsSection, LaboratoryofCellandDevelopmentalBiology, NIDCR,NIH,Bethesda,MD,USA2009-present ResearchassociateprofessorinTokyoDentaland MedicalUniversity,GCOEprogram (SectionofMaxillofacialOrthognathics)

Award and Honors

2004 FogartyInternationalCenterfellowshipawardforpost- doctoraltrainingattheNIH2007 Bestpresentationawardsattheannualmeetingof JapaneseOrthodonticSociety

Publications

1. HaruyamaN,IgarashiK,SaekiS,Otuka-IsoyaM,ShinodaH,MitaniH.Estrous-cycle-dependentVariationinOrthodonticToothMovement.JDentRes.2002Jun;81(6):406-10

2. LiuL,IgarashiK,HaruyamaN,SaekiS,ShinodaH,MitaniH. Effectsoflocaladministrationofclodronateonorthodontic

toothmovementsinrats. EurJOrthod.2004Oct;26(5):469-73.3. KanzakiH,ChibaM,TakahashiI,HaruyamaN,Nishimura

M,MitaniH. LocalOPGgenetransfertoperiodontaltissueinhibits

orthodontictoothmovement.JDentRes.2004Dec;83(12):920-5.

4. KanzakiH,ChibaM,AraiK,TakahashiI,HaruyamaN,NishimuraM,MitaniH.LocalRANKLgenetransfertotheperiodontaltissueacceleratesorthodontictoothmovement.

GeneTher.2006Apr;13(8):678-85.5. HatakeyamaJ,PhilpD,HatakeyamaY,HaruyamaN,Shum

L,AragonMA,YuanZ,GibsonCW,SreenathT,KleinmanHK,KulkarniAB.Amelogenin-mediatedRegulationofOsteoclastogenesis,andPeriodontalCellProliferationandMigration.JDentRes.2006Feb;85(2):144-9.

6. HaruyamaN,ThyagarajanT,SkobeZ,WrightJT,SeptierD,SreenathTL,GoldbergM,KulkarniAB.

Overexpressionoftransforminggrowthfactor-beta1inteethresultsindetachmentofameloblastsandenameldefects.EurJOralSci.2006May;114S1:30-4.

7. VerdelisK,LingY,SreenathT,HaruyamaN,MacdougallM,vanderMeulenMC,LukashovaL,SpevakL,KulkarniAB,BoskeyAL.

DSPPeffectsoninvivobonemineralization. Bone.2008Dec;43(6):983-908. ChoiSJ,RoodmanGD,FengJQ,SongIS,AminK,HartPS,

WrightJT,HaruyamaN,HartTC.Invivoimpactofa4bpdeletionmutationintheDLX3geneonbonedevelopment.DevBiol.2009Jan;325(1):129-37.

9. SatoS,TsuchiyaM,KomakiK,KusunokiS,TsuchiyaS,HaruyamaN,TakahashiI,SasanoY,WatanabeM.SynthesisandintracellulartransportationoftypeIprocollagenduringfunctionaldifferentiationofodontoblasts.HistochemCellBiol.2009May;131(5):583-91.[Epub2009Jan21]

10.HatakeyamaJ,FukumotoS,NakamuraT,HaruyamaN,SuzukiS,HatakeyamaY,ShumL,GibsonCW,YamadaY,KulkarniAB.SynergisticRolesofAmelogeninandAmeloblastin.JDentRes.2009Apr;88(4):318-322.

11.HaruyamaN*,SreenathTL*,SuzukiS,YaoX,WangZ,WangY,HoneycuttC,IozzoRV,YoungMF,KulkarniAB.*Authorsequallycontributed.Geneticevidenceforkeyrolesofdecorinandbiglycanindentinmineralization.MatrixBiol.2009Apr;28(3):129-136.

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12. SuzukiS,SreenathT,HaruyamaN,HoneycuttC,TerseA,ChoA,KohlerT,MüllerR,GoldbergM,KulkarniAB.

Dentinsialoproteinanddentinphosphoproteinhavedistinctrolesindentinmineralization.MatrixBiol.2009May;28(4):221-9.

13. SatoK,HaruyamaN,ShimizuY,HaraJ,KawamuraH. Osteogenesisbygraduallyexpandingtheinterface

betweenbonesurfaceandperiosteumenhancedbybonemarrowstemcelladministrationinRabbits.

OralSurgOralMedOralPatholOralRadiolEndod.2010July;110(1):32-40.

14.ChoiSJ,SongIS,FengJQ,GaoT,HaruyamaN,GautamP,RobeyPG,HartTC.

MutantDLX3disruptsodontoblastpolarizationanddentinformation.DevBiol.2010;Aug15;344(2):682-92.

15.ChoA,SuzukiS,HatakeyamaJ,HaruyamaN,KulkarniAB.

AMethodforRapidDemineralizationofTeethandBones. OpenDentJ.2010Dec15;4:223-229.16.MaD,ZhangR,RiosHF,HaruyamaN,SunY,XieY,

KulkarniAB,QinC,FengJQ. AnovelroleofPeriostininpostnataltoothformationand

mineralization.JBiolChem.2011Feb11;286(6):4302–09Epub2010Dec3.

17.TeraoF,TakahashiI,MitaniH,HaruyamaN,SasanoY,SuzukiO,Takano-YamamotoT.

Fibroblastgrowthfactor10regulatesMeckel'scartilageformationduringearly mandibularmorphogenesisinrats.

DevBiol.2011Feb15;350(2):337-47.Epub2010Dec11.18.HaruyamaN,HatakeyamaJ,MoriyamaK,KulkarniAB. Amelogenins:Multi-functionalenamelmatrixproteinsand

theirbindingpartners.JOralBiosci.2011Aug;53(3):257-66.19.QiuL,HaruyamaN,SuzukiS,YamadaD,ObayashiN,

KurabayashiT,MoriyamaK. Accuracyoforthodonticminiscrewimplantationguidedby

stereolithographicsurgicalstentbasedoncone-beamCTderived3Dimages.

AngleOrthod.2012Mar;82(2):284-93.20.TokugawaY,KubotaM,NishimuraM,HaruyamaN,

IgarashiK Boneregenerationofcanineartificialalveolarcleftsusing

bone-marrow-derivedmesenchymalstromalcellsandβ-tricalciumphosphate:Apreliminarystudy

OrthodWaves.2012June;71(2):51–5821. SuzukiS,HaruyamaN,NishimuraF,KulkarniAB. Dentinsialophosphoproteinanddentinmatrixprotein-1:

Twohighly phosphorylatedproteinsinmineralizedtissues.ArchOralBiol.inpress.

22.MitaniK*,HaruyamaN*,HatakeyamaJ,IgarashiK. *Authorsequallycontributed. Amelogeninspliceisoformsstimulatechondrogenic

differentiationofATDC5cells.OralDis.inpress.

Naoto Haruyama

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The periodontal - systemic connection: Molecular mechanisms and their significance in overall health care

Gregory J. Seymour, BDS, MDSc, Ph.D.

SirJohnWalshResearchInstitute,FacultyofDentistry,UniversityofOtago,NewZealand

Therelationshipbetweenpoororalhealthandsystemicdiseaseshas,overthelasttwodecades,beenincreasinglyrecognized.Alargenumberofepidemiologicalstudieshavenowclearlyestablishedthelinkbetweenpoororalhealthandcardiovasculardiseases,poorglycaemiccontrolindiabetics,aswellasanumberofotherdiseases.Thevastmajorityofstudiesinvestigatingtherelationshipbetweenperiodontaldiseaseandcardiovasculardiseaseshowasignificantpositiveassociationevenafteradjustingforconfounders,suchthatthefocusisnowonthebiologicalmechanismswhichunderpinthisrelationshipaswellasontheroleofperiodontaltreatmentinreducingtheriskoffurthercardiovascularevents.Anumberofhypotheseshavebeenpostulatedtoexplaintheassociationbetweenperiodontaldiseaseandatherosclerosis.Theseinclude(i)commonsusceptibilitywhichmayinvolveacommonsusceptibilitygene(s)butwherethereisnodirectlinkbetweenthetwodiseases,(ii)directinfectionofthearterialwallbyoralorganisms,includingtherecognisedperiodontalpathogens,followingbacteraemia,(iii)systemicinflammationandincreasedlevelsofcirculatingcytokineswithatherogenicpotentialandfinally(iv)molecularmimicrybetweenstressproteinsexpressedontheperiodontalbacteriaandheatshockprotein60(HSP60)expressedonstressedendothelialcells.Withrespecttothisfinalmechanism,antibodiestobothPorphyromonasgingivalisGroELantigenandhumanHSP60,whichcross-reactwithoneanother,havebeenidentifiedintheserumofpatientswithcardiovasculardisease,thelevelsofwhicharesignificantlycorrelatedwiththeextentofperiodontaldiseaseandwiththenumbersofperiodontalpathogens.Inaddition,cross-reactiveP.gingivalisGroELandHSP60specificTcellhavebeenidentifiedintheperipheralblood,aswellasintheatheroscleroticplaquesofpatientswithatherosclerosis.Thesedata,togetherwiththeobservationthatenhancedatherosclerosisinP.gingivalisinfectedApo-Edeficientmiceisassociatedwithincreasedlevelsofanti-P.gingivalisGroELantibodies,providestrongsupportfortheroleofmolecularmimicrycontributingtotheassociationbetweenperiodontaldiseaseandcardiovasculardisease.

Althoughanumberofstudieshaveshownanimprovementinendothelialfunctionfollowingperiodontaltherapy,thereisadistinctlackofevidenceshowingthatthetreatmentofperiodontaldiseaseimpactsonclinicalcardiovascularoutcomes.Suchstudies,bynecessity,needtoinvolveseveralthousandsubjectsfollowedoveralongperiodoftime–uptotenyearsandareprobablytooexpensiveandtoodifficulttoundertake.

Overallhowever,therelationshipbetweenpoororalhealthandsystemicdiseaseshasbecomeasignificantissue,anddespitethelackofdirectclinicalevidence,thereissufficientstrongbasicbiologicalevidencetoexplaintheunderlyingmechanism,suchthattheseassociationscannolongerbeignoredinoverallhealthstrategies.

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Gregory J. Seymour

CURRICULUM VITAE

Education

1971 BDS(honours),UniversityofSydney1974 MDSc(periodontology),UniversityofSydney Thesis:Gingivalfluid:itsnatureandmeasurement.1978 PhD,UniversityofLondon Thesis:Theimmunopathogenesisofchronic inflammatoryperio¬dontaldiseaseinman:Phenotypic chacterizationoflymphoidcellsubpopulationsinsitu usingenzymeandsurfaceantigenmarkers.1984 MRCPath,TheRoyalCollegeofPathologists,England1996 FRCPath,TheRoyalCollegeofPathologists,England1996 FFOP(RCPA),TheRoyalCollegeofPathologists Australasia2004 FRACDS(Perio),TheRoyalAustralasianCollegeof DentalSurgeonsPosition

1997-2003 Head,SchoolofDentistry,FacultyofHealth Sciences,TheUniversityofQueensland.1999-2001 DirectorofResearch,FacultyofHealthSciences, TheUniversityofQueensland2002-2008 ProfessorofOralBiology&Periodontology,The UniversityofQueensland2004-2005 GuestProfessor,FacultyofDentistry,The UniversityofBerne,Switzerland2004-2005 ConsultantPeriodontist,LoganHospital,Brisbane2005-present DeanFacultyofDentistryandProfessorof Periodontology,UniversityofOtago,NewZealand2008 VisitingProfessor,DepartmentofPeriodontology, UniversityofNebraska,Lincoln,Nebraska,U.S.A.2009-2010 DeputyProVice-Chancellor,DivisionofHealth Sciences,UniversityofOtago,NewZealand

Award and Honors

2003 FellowshipofthePierreFauchardAcademyFPFA2003 HonorarylifemembershipoftheBritishSocietyfor

Periodontology2003 MemberintheGeneralDivisionoftheOrderof

AustraliaforservicestodentistrythroughimmunologyandperiodontalresearchandthroughdentalandoralhealtheducationandadministrationAM

2004 HonorarylifemembershipoftheAustralianDentalAssociation(Queenslandbranch)forlonganddistinguishedservicetodentistry

2005 FellowshipoftheAcademyofDentistryInternationalFADI

2008 FellowshipoftheRoyalSocietyofNewZealandforoutstandingcontributiontoNewZealandscience.FRSNZ

Publications

BooksSEYMOURGJ,SAVAGENW,andWALSHLJ:1.Immunology:AnIntroductionfortheHealthSciences.McGrawHill.1995.SEYMOURGJ,CULLINANMP,HENGNEds;Oral2.BiologyMolecularTechniquesandApplications.MethodsinMolecularBiology666–HumanaPressTotowa,NJUSA2010

EditedJournalSEYMOURGJ&TAYLORJJEds;Immunoregulationin1.periodontaldisease.Periodontology2000Volume35:2004ARMITAGEGC,CULLINANMP,SEYMOURGJ2.Eds;ComparativeBiologyofChronicandAggressivePeriodontitis.Periodontology2000Volume53:2010

BookChapters1. GREAVESMF,WILLIAMSRCandSEYMOURGJ:

Assayforhumanlymphocytesubpopulations.In'CurrentResearchinRheumatoidArthritisandAlliedDiseases'Ed.D.C.DumondeandR.M.Maini.MedicalandTechnicalPublicationsPressLtd.England,1978.

2. POULTERLW,CHILOSIM,SEYMOURGJ,HOBBSSandJANOSSYG:ImmunofluorescenceMembraneStainingandCytochemistry,AppliedinCombinationforAnalyzingCellInteractionsinsitu.In:Polak,J.andvanNoorden,S.eds.ImmunocytochemistryPracticalApplicationsinPathologyandBiology1983;pp.23348.Bristol,WrightPSG.

3. SEYMOURGJ:Chronicinflammatoryperiodontaldiseaseintotaloralhealthcare.InCurrentAspectsofDentalHealth-aScientificApproach,1983;pp.1105.OralBFoundation,Australia.

4. WALSHLJ,SEYMOURGJandPOWELLRN:Interleukin-1andanInterleukin-1inhibitormodulateCD1antigenexpressiononaputativeintraepithelialLangerhanscellprecursorpopulation.In:"TheLangerhansCell".Eds.J.Thivolet&D.Schmitt.JohnLibbeyEurotext1988;172:231-239.

5. SEYMOURGJandFORDPJ.Theoralcavity.In:MucosalImmunology.Ed.A.W.Cripps.Newey&Beath,Newcastle.pp.143-148.

6. TAUBMANMA,WANGH-Y,LUNDQVISTCA,SEYMOURGJ,EASTCOTTJWandSMITHDJ.Thecellularbasisofhostresponsesinperiodontaldiseases.InPeriodontalDisease:Pathogens&HostImmuneResponses.Eds.S.Hamada,S.C.HoltandJ.R.McGhee.QuintessencePublishingCo.Ltd.Chicago,1991.

7. SYMONSAL,LEONGK,ZHANGCZ,YOUNGWG,WATERSMJandSEYMOURGJ:Thedistributionofgrowthhormonereceptorassociatedwithtoothdevelopmentintherat.inTheBiologicalMechanismsofToothEruption,ResorptionandReplacementbyImplants,ed.ZDavidovitch,305-316,HarvardSocietyforThe

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AdvancementofOrthodontics,Boston,1994.8. SEYMOURGJ,CULLINANMP,WESTERMANBand

GEMMELLE.RiskfactorsforperiodontaldiseaseinanAustralianpopulation.in"RiskFactorsinAsianPacificPopulations".1996.Ed.PMarkBartold.ProceedingsoftheAsianPacificSocietyofPeriodontology.Chapter11,92-103.

9. SYMONSAL,LEONGK,WATERSMJandSEYMOURGJ.Theeffectofgrowthhormoneonrootdevelopmentintheratmandibularmolar.BiologicalMechanismsofToothMovementandCraniofacialAdaptation.ZDavidovitchandLANortoneds.1996;449-457.HarvardSocietyfortheAdvancementofOrthodontics,Boston,Massachusetts,USA.

10.ASHMANRB,SEYMOURGJ.GeneralImmunology.In‘OxfordHandbookOfAppliedDentalSciences’Ed.CScully.OxfordUniversityPress,OxfordEngland,2002;pp434-447

11.ASHMANRB,SEYMOURGJ.Humoralandsolublemediatorsoftheimmuneresponse.In‘OxfordHandbookOfAppliedDentalSciences’Ed.CScully.OxfordUniversityPress,OxfordEngland,2002;pp450-459

12.ASHMANRB,SEYMOURGJ.Cell-mediatedimmunity.In‘OxfordHandbookOfAppliedDentalSciences’Ed.CScully.OxfordUniversityPress,OxfordEngland,2002;pp462-467

13.ASHMANRB,SEYMOURGJ.ClinicalImmunology.In‘OxfordHandbookOfAppliedDentalSciences’Ed.CScully.OxfordUniversityPress,OxfordEngland,2002;pp470-480.

14.FORDPJ,GEMMELLE,SEYMOURGJ.Theimmunopathologyofperiodontaldisease:linkswithatherosclerosis.MicrobiologyAustralia2005;26:127-129

15. SEYMOURGJ,CULLINANMP.Susecptibilitytoperiodontaldisease:Host,bacteriaandlifestyle.In:Shishubyogaku-NoShiten-KaraMitaKokumin-NoKenkozoshin–Nihonshishubyogakkai50Shunen.!stedition,Eds;TheJapaneseSocietyofPeriodontology.IshiyakuPublishers,Inc.TokyoJapan2008pp3-12

16. SEYMOURGJ,GEMMELLE,YAMAZAKIK.Tcellresponsesinperiodontitis.In:PeriodontalMedicineandSystemsBiology.Eds;HendersonB,CurtisM,SeymourRA,DonosN.Wiley-BlackwellPublishingLimited,ISBN:978-1-4051-2219-1,OxfordUK;2009pp357-376

17. SEYMOURGJTheGenesisofanidea.In:OralHealthTherapyProgramsinAustraliaandNewZealand.Ed:TsangAKL.KnowledgeBooksandSoftware,VarsityLakes,Queensland,Australia.2010:pp29-32.

Papers(Publishedoracceptedforpublication)

CHOIJ-I,SEYMOURGJVaccinesagainstperiodontitis:1.aforward-lookingreview.JPeriodontalImplantSci2010;40:153-163LOYOLA-RODRIGUEZJP,MARTINEZ-MARTINEZRE,2.ABUD-MENDOZAC,PATIÑO-MARINN,SEYMOURGJRheumatoidarthritisandtheroleoforalbacteria.Journal

ofOralMicrobiology2010;2:5784-DOlDESAISV,LOVERM,RICHAM,SEYMOURGJ.3.Antigenrecognitionandpresentationinperiapicaltissues:AroleforTLRexpressingcells.InternationalEndodonticJournal2011;44:87–99.NGLK,RICHAM,HUSSAINIHM,THOMSONWM,4.FISHERAL,HORNELS,SEYMOURGJ.Toll-likereceptor2ispresentinthemicroenvironmentoforalsquamouscellcarcinoma.BritishJournalofCancer2011;104:460-463.ANDERSONV,RICHAM,SEYMOURGJ.Undergraduate5.dentaleducationinNewZealand:2007-2009final-yearstudentfeedbackonclinicallearningenvironmentsNewZealandDentalJournal2011;107:85-90.HUSSAINIHM,WADDELLJN,GIRVANL,WESTLM,6.KARDOSTB,RICHAM,SEYMOURGJ.Silversolder'tattoo',anovelformoforalpigmentationidentifiedusingSEM-EDSOralSurgery,OralMedicine,OralPathology,OralRadiologyandEndodontology2011;112:6-10DESAISV,LOVERM,RICHAM,SEYMOURGJ.Toll-7.likereceptor2expressioninrefractoryperiapicallesions.InternationalEndodonticJournal2011;44:907-916ROSE-HILLS,FORDPJ,LEISHMANS,DOHL,8.PALMERJE,HENGNCK,WESTMJ,SEYMOURGJ.CULLINANMP.ImprovedperiodontalhealthandcardiovascularriskAustralianDentalJournal2011;56:352-357SOSROSENOW,BIRDPS,SEYMOURGJ.Nitric9.oxideproductionbyamurinemacrophagecellline(RAW264.7cells)stimulatedwithAggregatibacteractinomycetemcomitanssurfaceassociatedmaterial.Anaerobe2011;17:246-251SINONSH,RICHAM,HUSSAINIHM,YOONH-S,10.FIRTHNA,SEYMOURGJMetastasestotheoralregionfrompleuralmesothelioma.Head&Neck2011;(inpress)CULLINANMP,PALMERJE,CARLEAD,WEST11.MJ,SEYMOURGJLongtermuseoftriclosantoothpasteandthyroidfunction.Scienceofthetotalenvironment2012;416:75-79GREGORYJ,THOMSONWM,BROUGHTONJR,12.CULLINANMP,SEYMOURGJ,KIESERJA,DONAGHYM-A,SHEARERDM.ExperiencesandperceptionsoforalhealthandoralhealthcareamongasampleofolderNewZealanders.Gerodontology2012;29:54-63RICHAM,AYERSK,THOMSONWM,SEYMOUR13.GJ.Doesperformanceinselectionprocessespredictperformanceasadentalstudent?EuropeanJournalofDentalEducation.2011;16:27-34SOOL,LEICHTERJW.WINDLEJ,MONTEITHB,14.WILLIAMSSM,SEYMOURGJ,CULLINANMP.AcomparisonofEr:Yaglaserandmechanicaldebridementforthenon-surgicaltreatmentofchronicperiodontitis:Arandomized,prospectiveclinicalstudy.JournalofClinicalPeriodontology2012;doi:10.1111/j.1600-051X.2012.01873.x.

Gregory J. Seymour

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Oral - Systemic Connection: Roles of the Host Factors

Nawarat Wara-aswapati, D.D.S., DMSc.

DepartmentofPeriodontology,FacultyofDentistry,KhonKaenUniversity,KhonKaen,Thailand

Periodontitisisaninflammatorydiseasecausedbygram-negativeperiodontopathicbacteria

whichcaninducetheproductionofhostinflammatorymediators,eventuallyleadingtothe

breakdownoftooth-supportingtissues.Emergingevidencehassuggestedtheassociation

ofperiodontaldiseaseswithseveralsystemicdiseasessuchasdiabetesmellitus(DM),

cardiovasculardiseases(CVDs),adversepregnancyoutcomes,respiratorydiseases,Alzheimer’

sdiseaseandcancer.Hostimmuneresponsesplayavitalroleintheperiodontal-systemic

connection.

Inthislecture,wewilldiscusstheassociationofhostfactors,Wnt5aandtrefoilfactors(TFFs),

withperiodontitis.Wnt5aissecretedbyactivatedantigen-presentingcellsandWnt5asignaling

isessentialforthegeneralinflammatoryresponseofhumanmacrophagesduringsepsis.TFFs

aresecretedmoleculesinvolvedincytoprotectionagainsttissuedamageandimmuneresponse.

Recently,wehaveinvestigatedthemechanismsbywhichP.gingivalismodulatesWnt5a

expression.Inaddition,wedeterminedifTFFexpressioninsalivaandgingivaltissueswas

associatedwithperiodontalpathology.OurresultssuggestedthatWnt5aandTFF3maybe

involvedinthepathogenesisofperiodontaldiseaseandplayaroleintheperiodontal-systemic

connection.

42

Nawarat Wara-aswapati

CURRICULUM VITAE

Education

1987-1993 D.D.S.(1stClassHonors) FacultyofDentistry,KhonKaenUniversity KhonKaen,Thailand1994-1998 DoctorofMedicalSciences(DMSc)inOral Biology CertificateinPeriodontology HarvardSchoolofDentalMedicine HarvardUniversity Boston,MA,USA.2003-present Diplomate,TheThaiBoardofPeriodontology, Thailand2003-present Diplomate,TheAmericanBoardof Periodontology,USAPosition

2001-2004 AssistantProfessorofPeriodontology FacultyofDentistry,KhonKaenUniversity, KhonKaen,Thailand2003-present AssistanttothePresident-InternationalAffairs OfficeofthePresident,KhonKaenUniversity KhonKaen40002,Thailand2005-present AssociateProfessorofPeriodontology FacultyofDentistry,KhonKaenUniversity, KhonKaen,Thailand2005-2006 ActingDirector(FoundedActingDirector) LanguageInstitute,KhonKaenUniversity, Thailand2006-2007 Director(FoundedDirector) ConfuciusInstituteatKhonKaenUniversity KhonKaenUniversity,Thailand2008-2009 VisitingProfessor DepartmentofHardTissueEngineering (Periodontology) FacultyofDentistry,TokyoMedicalandDental UniversityJapan

Award and Honors

2002 TheJSPS-NRCTscholarship ForresearchatTokyoMedicalandDentalUniversity Japan2004 Theshort-termvisitinglecturergrant CenterforExcellenceProgramforFrontierResearch onMolecularDestructionandReconstructionofTooth andBoneTokyoMedicalandDentalUniversity,Japan2005“Paperoftheweek”JournalofBiologicalChemistry2008 JSPSInvitationFellowshipProgramforResearchin Japan(LongTerm)2009 DistinguishedAlumniAward FacultyofDentistry,KhonKaenUniversity,Thailand

Publications

ZhangP,BehreG,PanJ,IwamaA,Wara-aswapatiN,1.RadomskaHS,AuronPE,TenenDG,andSunZ.NegativeCross-TalkBetweenHematopoieticRegulations:GATAproteinsrepressPU.1.Proc.Natl.Acad.Sc.USA1999;96:8705-8710Wara-aswapatiN,HowellHT,NeedlemanHL,and2.KarimbuxN.PeriodontitisintheChildandAdolescent.ASDCJ.DentChild.1999;66:167-174.Wara-aswapatiN,KoyamaY,WatermanWR,Tetradis3.S,ChoyBK,WebbAC,andAuronPE.HumanCytomegalovirusIE2ProteinUpregulatesHumanProinterleukin1 βGeneExpressionviaProtein-TetheredTransactivation.Mol.CellBiol.1999;19:6803-6814YangZ,Wara-AswapatiN,ChenC,TsukadaJ,AuronPE.4.NF-IL6(C/EBPbeta)vigorouslyactivatesIL-1 βgeneexpressionviaaspi-1(PU.1)protein-proteintether.JBiolChem2000Jul14;275(28):21272-7BochJ,Wara-aswapatiN,AuronPE.Interleukin15.signaltransduction-currentconceptsandimportanceinperiodontitis.JDentRes2001;80(2):400-7.Wara-aswapatiN,PitiphatW,ChandraphoN,6.RattanayatikulCandKarimbuxN.ThicknessofPalatalMasticatoryMucosaAssociatedwithAge.JPeriodontol2001;72:1407-1412.Wara-aswapatiN,LertsirivorakulJ,NagasawaT,7.KawashimaYandIsaoIshikawa.Papillon-LefevreSyndrome:SerumImmunoglobulinG(IgG)SubclassAntibodyResponsetoPeriodontopathicBacteria.ACaseReportJPeriodontol2001;72:1747-1754.Wara-aswapatiN.ClassificationofPeriodontalDiseasesand8.Conditions.KhonKaenDentJ2001;4:15-22.KrongnawakulD,andWara-aswapatiN.Roleof9.Interleukin-1GenotypeinPeriodontalDisease.JDentAssocThai2002;52:133-139YangZ,Wara-aswapatiN,YoshidaY,WalkerN,Galson10.DL,ListmanJandAuronPE.Dualregulatoryroleofhumancytomegalovirusimmediate-earlyproteinonIL-1BtranscriptionisdependentuponSpi-1/Pu.1.BiochemBiophyResCom2002;294:854-63Wara-aswapatiN,BochJ,AuronPE.Activation11.ofInterleukin1 βGeneTranscriptionbyHumanCytomegalovirus—MolecularMechanismsandRelevancetoPeriodontitis.Mini-Review.OralMicrobiolImmunol2003:18;67-71.BochJ,YoshidaY,KoyamaY,Wara-AswapatiN,PengH,12.UnluS,AuronPE.CharacterizationofacascadeofproteininteractionsinitiatedattheIL-1receptor.BiochemBiophyResCom2003;525-531.Wara-aswapatiN,KrongnawakulD,JiraviboonD,13.AdulyanonS,KarimbuxN,PitiphatW.Theeffectofanewtoothpastecontainingpotassiumnitrateandtriclosanongingivalhealth,plaqueformationanddentinehypersensitivity.JClinPeriodontol.2005Jan;32(1):53-8.

43

NittaH,Wara-aswapatiN,LertsirivorakulJ,NakamuraT,14.YamamotoM,IzumiY,NakamuraT,IshikawaI.AnovelmutationofthecathepsinCgeneinaThaifamilywithPapillon-Lefvresyndrome.JPeriodontol2005March;76(3):492-496.ListmanJA,Wara-aswapatiN,RaceJE,Blystone15.LW,Walker-KoppN,YangZ,AuronPE.ConservedETSdomainargininesmediateDNAbinding,nuclearlocalizationandanovelmodeofbZIPinteraction.JBiolChem2005Dec16;280(50):41421-8.WangKZQ,Wara-AswapatiN,BochJA,YoshidaY,Hu16.CD,GalsonDL,AuronPE.TRAF6ActivationofPI3Kinase-DependentCytoskeletalChangesisCooperativewithRasandMediatedbyanInteractionwithCytoplasmicc-Src.JournalofCellScience2006Apr15;119(8):1579-91.TaweechaisupapongS,IntaranongpaiK,Suwannarong17.W,PitiphatW,ChatrchaiwiwatanaS,Wara-aswapatiN.ClinicalandmicrobiologicaleffectsofsubgingivalirrigationwithStreblusasperleafextractinchronicperiodontitis.JClinDent.2006;17(3):67-71.Wara-aswapatiN,SuraritR,ChayasadomA,BochJA,and18.PitiphatW.ReceptorActivatorofNuclearFactor-KappaBLigandUpregulationAssociatedwithPeriodontitisandPorphyromonasgingivalis.J.Periodontol2007;78(6):1062-69.PitiphatW,SavetsilpW,andWara-aswapatiN.C-reactive19.ProteinAssociatedwithPeriodontitisinaThaiPopulation.JClinPeriodontol.2008;35(2):120-5.JongyotaW,WigraipatC,NontapaS,TaweechaisupapongS,20.Wara-AswapatiN,WongratanacheewinS,SermswanRW.DifferentialresponseofcytokinesinducedbyLeptospirainterrogans,serogroupPomona,serovarPomona,inmouseandhumancelllines.AsianPacJAllergyImmunol.2008;26(4):229-36.Wara-AswapatiN,PitiphatW,ChanchaimongkonL,21.TaweechaisupapongS,BochJA,IshikawaI.RedbacterialcomplexisassociatedwiththeseverityofchronicperiodontitisinaThaipopulation.OralDis.2009;15:354-59SripanidkulchaiB,JunlatatJ,Wara-AswapatiN,Hormdee22.D.Anti-inflammatoryeffectofStreblusasperleafextractinratsanditsmodulationoninflammation-associatedgenesexpressioninRAW264.7macrophagecells.JEthnopharmacol.2009Jul30;124(3):566-70ChenYW,NagasawaT,Wara-AswapatiN,UshidaY,23.WangD,TakeuchiY,KobayashiH,UmedaM,InoueY,IwaiT,IshikawaI,IzumiY.Associationbetweenperiodontitisandanti-cardiolipinantibodiesinBuergerdisease.JClinPeriodontol.2009Aug12.[Epubaheadofprint]SudaT,NagasawaT,Wara-aswapatiN,KobayashiH,24.IwasakiK,YashiroR,HormdeeD,NittaH,IshikawaI,IzumiY.Regulatoryrolesofβ -cateninandAP-1onOPGproductioninIL-1 α -stimulatedperiodontalligamentcells.OralMicrobiolImmunol2009Oct;24(5):384-9.IzumiY,NagasawaT,UmedaM,KobayashiH,TakeuchiY,25.

YashiroR,HormdeeD,SudaT,UshidaY,Wara-aswapatiN.Periodontitisandcardiovasculardiseases:Thelinkandrelevantmechanisms.JapaneseDentalScienceReview(2009)45,98-108.AemaimananP,SattayasaiN,Wara-aswapatiN,Pitiphat26.W,SuwannarongW,PrajanehS,TaweechaisupapongS.AlanineaminopeptidaseanddipeptidylpeptidaseIVinsalivaofchronicperiodontitispatients.JPeriodontol.2009Nov;80(11):1809-14.NagasawaT,NodaM,KatagiriS,TakaichiM,Takahashi27.Y,Wara-AswapatiN,KobayashiH,OharaS,KawaguchiY,TagamiT,FuruichiY,IzumiY.Relationshipbetweenperiodontitisanddiabetes-importanceofaclinicalstudytoprovetheviciouscycle.InternMed.2010;49(10):881-5.SuJ,SripanidkulchaiB,SripanidkulchaiK,Piyachaturawat28.P,Wara-AswapatiN.EffectofCurcumacomosaandestradiolonthespatialmemoryandhippocampalestrogenreceptorinthepost-trainingovariectomizedrats.JNatMed.2011Jan;65(1):57-62.IzumiY,AokiA,YamadaY,KobayashiH,IwataT,29.AkizukiT,SudaT,NakamuraS,Wara-AswapatiN,UedaM,IshikawaI.Currentandfutureperiodontaltissueengineering.Periodontol2000.2011Jun;56(1):166-87.ChaiyaritP,ChayasadomA,Wara-AswapatiN,HormdeeD,30.SittisomwongS,NakaresisoonS,SamsonMH,PitiphatW,GiraudAS.TrefoilFactorsinSalivaandGingivalTissuesofPatientsWithChronicPeriodontitis.JPeriodontol.2011Dec19.[Epubaheadofprint]NanbaraH,Wara-aswapatiN,NagasawaT,YoshidaY,31.YashiroR,BandoY,KobayashiH,KhongcharoensukJ,HormdeeD,PitiphatW,BochJA,IzumiY.ModulationofWnt5aexpressionbyperiodontopathicbacteria.PLoSOne.2012;7(4):e34434.Epub2012Apr2.

Nawarat Wara-aswapati

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The biologic effect of oligopeptides derived from fibronectin and its application to biomimetics

Young Ku, D.D.S., Ph.D.

DepartmentofPeriodontology,SchoolofDentistry,SeoulNationalUniversity,Seoul,Korea

Fibronectin(FN)isamajorglycoproteinintheextracellularmatrix(ECM)andregulatesvarious

cellularevents.Itisconsistedofdisulfide-linked235kDamonomers,whicharecomposedof

threedomains;typesI,IIandIII.TheArg-Gly-Asp(RGD)andPro-His-Ser-Arg-Asn(PHSRN)in

10thand9thtypeIIIdomain,respectively,areimportantcelladhesion.Oligopeptidesbasedon

FNareregardedasattractivebiomoleculesforbiomaterials.WesynthesizedFNtypeIII7-10,

8-10and9-10fragmentsandanalyzedtheirbiologicactivities.WealsosynthesizedPHSRNand

RGDcontainingshortoligopeptideswithlinkersandalsoviarecombinantDNAtechnologyand

investigatedtheirbiologicaleffects.Recentlyweevaluatedtheoligopeptidesfromfibrinbinding

domainbasedonFNandfoundthatthesepeptideshaveenhancingbiologicactivitiesinsome

celllines.Wehypothesizedthatthesepeptidescanbeusedasbiomaterialsurfacemodifiers

whichcouldenhancebiocompatibilityandwoundhealing.

46

Young Ku

CURRICULUM VITAE

Education

1980-1982 Predentalcourse,CollegeofNatural Science,SeoulNationalUniversity(S.N.U.)1982-1986 D.D.S.:CollegeofDentistry,S.N.U.1988-1993 M.S.:GraduateSchool,S.N.U.1994-1997 Ph.D:Graduateschool,S.N.U.

Position

1996-2009 Fulltimeinstructor,Assistantprofessor, Associateprofessor,SchoolofDentistry,S.N.U.2009-present ProfessorandChairman,Departmentof Peridontology,SchoolofDentistry,S.N.U.1999-2000 VisitingProfessor,DepartmentofPeriodontology, SchoolofDentistry,UniversityofNorthCarolina atChapelHill,N.C.,U.S.A.2004 VisitingProfessor,DepartmentofPeriodontology, RoyalCollegeofDentistry,AarhusUniversity, Denmark2004 Director,ImplantCenter,SeoulNational UniversityDentalHospital2005-present AdjunctProfessor,DepartmentofPeriodontology, UniversityofPennsylvania2005-2006 AssociateDeanofStudentAffairsandPlanning, SchoolofDentistry,SeoulNationalUniversity2008-2010 AssociateDeanofStudentAffairs,SeoulNational University2010-2010 VisitingProfessor,DepartmentofPeriodontology, TokyoMedicalandDentalUniversity,Japan

Publications

1. SeolYJ,LeeJY,ParkYJ,LeeYM,Young-Ku,RhyuIC,LeeSJ,HanSB,ChungCP.Chitosanspongesastissueengineeringscaffoldsforboneformation.BiotechnolLett.2004Jul;26(13):1037-41.

2. YangSM,KimSY,LeeSJ,LeeYK,LeeYM,KuY,ChungCP,HanSB,RhyuIC.Tissueresponseofcalciumpolyphosphateinbeagledog,PartII;12monthsresult.KeyEngMat2004;254-256:245-248.

3. KimY,JangJH,KuY,KoakJY,ChangIT,KimHE,LeeJB,HeoSJMicroarray-basedexpressionanalysisofhumanosteoblast-likecellresponsetoanodizedtitaniumsurface..BiotechnolLett.2004Mar;26(5):399-402

4. LeeJY,LeeYM,ShinSY,SeolYJ,KuY,RhyuIC,ChungCP,HanSB.Effectofsubantimicrobialdosedoxycyclineasaneffectiveadjuncttoscalingandrootplanning.JPeriodontol.2004Nov;75(11):1500-8

5. YKu,CPChung,JHJang.Theeffectofthesurfacemodificationoftitaniumusingarecombinantfragmentoffibronectinandvitronectinoncellbehavior.Biomaterials2005;26(25):5153-5157

6. ParkYJ,KimKH,LeeJY,KuY,LeeSJ,MinBM,ChungCP.Immobilizationofbonemorphogeneticprotein-2ontoananofibrouschitosanmembraneforenhancedguidedboneregeneration.BiotechnolApplBiochem.2006Jan;43(Pt1):17-24

7. KimKH,JeongL,ParkHN,ShinSY,ParkWH,LeeSC,KimTI,ParkYJ,SeolYJ,LeeYM,KuY,RhyuIC,HanSB,ChungCP..Biologicalefficacyofsilkfibroinnanofibermembranesforguidedboneregeneration.JBiotechnol.2005;120(3):327-339

8. ShinSY,ParkHN,KimKH,LeeMH,ChoiYS,ParkYJ,LeeYM,KuY,RhyuIC,HanSB,LeeSJ,ChungCP.Biologicalevaluationofchitosannanofibermembraneforguidedboneregeneration.JPeriodontol.2005Oct;76(10):1778-84.

9. SeolYJ,ParkYJ,LeeSC,KimKH,LeeJY,KimTI,LeeYM,KuY,RhyuIC,HanSB,ChungCP.Enhancedosteogenicpromotionarounddentalimplantswithsyntheticbindingmotifmimickingbonemorphogeneticprotein(BMP)-2.JBiomedMaterResA.2006Jun1;77(3):599-607.

10. LeeYM,ShinSY,KimJY,KyeSB,KuY,RhyuIC.Bonereactiontobovinehydroxyapatiteformaxillarysinusflooraugmentation:histologicresultsinhumans.IntJPeriodonticsRestorativeDent.2006Oct;26(5):471-81.

11. ParkJB,LeeJY,ParkHN,SeolYJ,ParkYJ,RheeSH,LeeSC,KimKH,KimTI,LeeYM,KuY,RhyuIC,HanSB,ChungCP.OsteopromotionWithSyntheticOligopeptide-CoatedBovineBoneMineralInVivo.JPeriodontol.2007Jan;78(1):157-163.

12.KimTI,LeeG,JangJH,ChungCP,KuY.InfluenceofRGD-containingoligopeptide-coatedsurfaceonboneformationinvitroandinvivo.BiotechnolLett.2007

47

Mar;29(3):359-363.13. ParkJB,LeeJY,ParkYJ,RheeSH,LeeSC,KimTI,

SeolYJ,LeeYM,KuY,RhyuIC,HanSB,ChungCP.EnhancedBoneRegenerationinBeagleDogsWithBovineBoneMineralCoatedWithaSyntheticOligopeptide.JPeriodontol.2007Nov;78(11):2150-2155.

14.KimHY,LeeSW,ChoSI,PattonL,KuY.AssociationsbetweenteethwithunmetneedsandsocioeconomicstatusamongSouthKoreandentategovernmentemployees.JPublicHealthDent.2007Summer;67(3):174-178.

15. SeolYJ,KimKH,ParkYJ,LeeYM,KuY,RhyuIC,LeeSJ,HanSB,ChungCP.Osteogeniceffectsofbonemorphogeneticprotein-2plasmidgenetransfer.BiotechnolApplBiochem.2008Jan.49:85-96.

16.KuY,ShimIK,LeeJY,ParkYJ,RheeSH,NamSH,ParkJB,ChungCP,LeeSJ.Chitosan/poly(L-lacticacid)multilayeredmembraneforguidedtissueregeneration.2008July9.JBiomedMaterResA

17.HwangYJ,FienMJ,LeeSS,KimTI,SeolYJ,LeeYM,KuY,RhyuIC,ChungCP,HanSB.EffectofScalingandRootPlaningonAlveolarBoneasMeasuredbySubtractionRadiographyJPeriodontol.2008Sep.79(9):1663-1669.

18.KimTI,JangJH,KimHW,KnowlesJC,KuY.BiomimeticApproachtoDentalImplants.CurrPharmDes.2008;14(22):2201-2211.

19. ParkOJ,ShinSY,ChoiY,KimMH,ChungCP,KuY,KimKK.Theassociationofosteoprotegeringenepolymorphismswithperiodontitis.OralDis.2008Jul;14(5):440-444

20.KimSH,KimDY,KimKH,KuY,RhyuIC,LeeYM.Theefficacyofadouble-layercollagenmembranetechiniqueforoverlayingblockgraftinarabbitcalvariummodel.ClinOralImplnatsRes.2009Oct;20(10):1124-1132.

21.KimSH,KimKH,SeoBM,KooKT,KimTI,SeolYJ,KuY,RhyuIC,ChungCP,LeeYM.Alveolarboneregenerationbytransplantationofperiodontalligamentstemcellsandbonemarrowstemcellsinacanineperi-implantdefectmodel:apilotstudy.JPeriodontol.2009Nov;80(11):1815-23.

22.KimHY,JangMS,BaikDI,ChungCP,ParkDY,PattenL,KuY.Chewingfunctionimpactsoralhealth-relatedqualityoflifeamonginstitutionalizedandcommunity-dwellingKoreanelders.CommunityDentOralEpidemiol2009;37:468-476.

23. ShinJH,KimKH,KimSH,KooKT,KimTI,SeolYJ,KuY,RhyuIC,ChungCP,LeeYM.Exvivobonemorphogeneticprotein-2genedeliveryusinggingivalfibroblastspromotesboneregenerationinrats.JClinPeriodontol.2010Mar;37(3):305-11.

24. LeeSY,PiaoCM,KoakJY,KimSK,KimYS,KuY,RhyuIC,HanCH,HeoSJ.A3-yearprospectiveradiographicevaluationofmarginalbonelevelarounddifferentimplantsystems.JOralRehabil.2010Apr9.

25.KooKT,WikesjöUM,ParkJY,KimTI,SeolYJ,KuY,RhyuIC,ChungCP,LeeYM.EvaluationofSingle-ToothImplantsintheSecondMolarRegion.A5-YearLifeTable

AnalysisofaRetrospectiveStudy.JPeriodontol.2010May3.26. LeeDH,KuY,RhyuIC,HongJU,LeeCW,HeoMS,Huh

KH.Aclinicalstudyofalveolarbonequalityusingthefractaldimensionandtheimplantstabilityquotient.JPeriodontalImplantSci.2010Feb;40(1):19-24.

27.ChoiEJ,YimJY,KooKT,SeolYJ,LeeYM,KuY,RhyuIC,ChungCP,KimTI.Biologicaleffectsofasemiconductordiodelaseronhumanperiodontalligamentfibroblasts.JPeriodontalImplantSci.2010Jun;40(3):105-10.

28. LeeDW,KooKT,SeolYJ,LeeYM,KuY,RhyuIC,ChungCP,KimTI.Boneregenerationeffectsofhumanallogenousbonesubstitutes:apreliminarystudy.JPeriodontalImplantSci.2010Jun;40(3):132-8.

29. LeeDW,KooKT,SeolYJ,LeeYM,KuY,RhyuIC,ChungCP,KimTI.Boneregenerationeffectsofhumanallogenousbonesubstitutes:apreliminarystudy.JPeriodontalImplantSci.2010Jun;40(3):132-8.

30. LeeJA,KuY,RhyuIC,ChungCP,ParkYJ.Effectsoffibrin-bindingoligopeptideonosteopromotioninrabbitcalvarialdefects.JPeriodontalImplantSci.2010Oct;40(5):211-9.

31. ParkJY,KooKT,KimTI,SeolYJ,LeeYM,KuY,RhyuIC,ChungCP.Socketpreservationusingdeproteinizedhorse-derivedbonemineral.JPeriodontalImplantSci.2010Oct;40(5):227-31.

32. LeeCK,KooKT,KimTI,SeolYJ,LeeYM,RhyuIC,KuY,ChungCP,ParkYJ,LeeJY.Biologicaleffectsofaporcine-derivedcollagenmembraneonintrabonydefects.JPeriodontalImplantSci.2010Oct;40(5):232-8.

33.OhHJ,WikesjöUM,KangHS,KuY,EomTG,KooKT.Effectofimplantdrillcharacteristicsonheatgenerationinosteotomysites:apilotstudy.ClinOralImplantsRes.2010Dec9.

34.KimHS,KimKH,KimSH,KimYS,KooKT,KimTI,SeolYJ,KuY,RhyuIC,ChungCP,LeeYM.Immunomodulatoryeffectofcanineperiodontalligamentstemcellsonallogenicandxenogenicperipheralbloodmononuclearcells.JPeriodontalImplantSci.2010Dec;40(6):265-70.

35. LeeEJ,KooKT,KimJY,SeolYJ,HanJS,KimTI,LeeYM,KuY,WikesjöUM,RhyuIC.Theeffectofinernalversusexternalabutmentconnectionmodesoncrestalbonechangesarounddentalimplants:aradiographicanalysis.JPeriodontol2011Dec.

36.NamHW,ParkJB,LeeJY,RheeSH,LeeSC,KooKT,KimTI,SeolYJ,LeeYM,KuY,RhyuIC,ParkYJ,ChungCP.Enhancedridgepreservationbybonemineralboundwithcollagen-bindingsyntheticoligopeptides:aclinicalandhistologicstudyinhumans.JPeriodontol2011Mar:82(3)

37.ByunYK,KimKH,KimSH,KimYS,KooKT,KimTI,SeolYJ,KuY,RhyuIC,LeeYM.Effectsofimmunosuppressants,FK506andcyclosporineA,ontheosteogenicdifferentiationofratmesenchymalstemcells.JPeriodontalImplantSci.2012Jun;42(3):73-80.

Young Ku

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Periodontal disease and atherothrombotic diseases: Lessons from clinical and basic studies

Kazuhisa Yamazaki, D.D.S., Ph.D.

LaboratoryofPeriodontologyandImmunology,DivisionofOralScienceforHealthPromotion,NiigataUniversityGraduateSchoolofMedicalandDentalSciences

Overthepasttwodecades,therelationshipbetweenpoororalhealthandsystemicdiseaseshasbeenincreasinglyrecognized.Thereisconsiderableepidemiologicalevidencetosupporttheconceptthatpoororalhealthmayputpatientsatasignificantriskforavarietyofsystemicconditionssuchascoronaryheartdisease(CHD).CHDistheleadingcauseofdeathinJapanandotherdevelopedcountries.ThemajorpathwayunderlyingCHDpathologyisatherosclerosis.Severalriskfactorsforatherosclerosishavebeenidentified,includingsmoking,hypertension,hyperglycemia,hypercholesterolemiaandgeneticfactors.However,atherosclerosiscandevelopintheabsenceoftheseclassicriskfactors.Recentepidemiologicalstudieshavesuggestedalinkbetweenatherosclerosisandinfection/inflammation.AssociationshavebeenreportedwithChlamydiapneumoniae,Helicobacterpylori,andcytomegalovirus,aswellaswithdentalinfections,particularlythoseassociatedwithperiodontitis.Severalbiologicallyplausiblemechanismshavebeenpresentedtoexplaintheassociation,suchasbacteremia,elevatedlevelsofinflammatorymarkers,generationofcross-reactiveimmuneresponsesbychronicinfections,andinductionofimbalancedcholesterolmetabolism.Thereisevidencedemonstratingthedirecteffectofperiodontopathicbacteriaonhostcells,increasedlevelsofhigh-sensitivityC-reactiveproteinandelevatedlevelsofcross-reactiveantibodybetweenhumanheat-shockprotein60anditsorthologue,GroELofPorphyromonasgingivalis.WehavedemonstratedthatP.gingivalisinducesseveralatherosclerosis-relatedmoleculesinhumancoronaryarterialendothelialcells,andthathigh-sensitivityC-reactiveprotein(hs-CRP)andinterleukin(IL)-6proteinlevelsarehigherincasesofperiodontitisandthatsuccessfultreatmentofperiodontitisdecreasesthelevelsofbothmediators.Inaddition,periodontitispatientshaveloweranti-atherogenicHDLcholesterolsthanperiodontallyhealthysubjects.However,sincethetwodisordersshareseveralcommonriskfactors,includingcigarettesmoking,age,anddiabetesmellitus,andmoreover,currentresearchdoesnotyetprovideevidenceofacausalrelationshipbetweenthetwodiseases,mediaclaimaboutanassociationbetweenperiodontitisandheartdisease.Nevertheless,severalanimalstudiesaimedatclarifyingtheeffectofperiodontopathicbacterialinfectiononatherogenesishavesuccessfullyshowntheformationofatheromatousplaqueandtheelevationofsystemicinflammatorymarkers.Recently,wehaveshownbyusingmousemodelthatperiodontalinfectionitselfdoesnotcauseatherosclerosis,butitacceleratesitbyinducingsystemicinflammationanddeterioratinglipidmetabolism,particularlywhenunderlyinghyperlidemiaorsusceptibilitytohyperlipidemiaexists.Inthispresentation,anupdateonthecurrentunderstandingofthecontributionofpoororalhealthtoatherosclerosisandthepossiblemechanismsinvolvedwillbepresentedanddiscussedbasedmainlyonourstudies.

50

Kazuhisa Yamazaki

CURRICULUM VITAE

Education

1974-1980 KanagawaDentalCollege AwardedthedegreeofD.D.S.1980-1985 DepartmentofPeriodontology,NiigataUniversity GraduateSchoolofDentistry AwardedthedegreeofPh.D.inDentistry1985-1988 AssistantProfessor,NiigataUniversityDental Hospital1988-1999 SeniorLecturer,NiigataUniversityDentalHospital1999-2004 AssociateProfessor,DivisionofPeriodontology, DepartmentofOralBiologicalScience,Niigata UniversityGraduateSchoolofMedicalandDental Sciences2004-2010 Professor,DepartmentofOralHealthandWelfare, NiigataUniversityFacultyofDentistry2006-present Professor,CenterforTransdisciplinary Research,NiigataUniversity2010-present Professor,LaboratoryofPeriodontologyand Immunology,DivisionofOralScienceforHealth Promotion,NiigataUniversityGraduateSchoolof MedicalandDentalSciences

Publications

1. MaeakawaT,TakahashiN,HondaT,YonezawaD,MiyashitaH,OkuiT,TabetaK,YamazakiK.Porphyromonasgingivalisantigensandinterleukin-6stimulatetheproductionofmonocytechemoattractantprotein-1viatheup-regulationofearlygrowthresponse-1transcriptioninhumancoronaryarteryendothelialcells.JVascRes47(4):346-354,2010.

2. TakahashiN,HondaT,DomonH,NakajimaT,TabetaK,YamazakiK.IL-1receptor-associatedkinase-MingingivalepithelialcellsattenuatestheinflammatoryresponseelicitedbyPorphyromonasgingivalis.J.PeriodontRes45(4):512-519,2010.

3. AokiY,TabetaK,MurakamiY,YoshimuraF,YamazakiK.AnalysisofimmunostimulatoryactivityofPorphyromonasgingivalisfimbriaeconferredbyToll-likereceptor2.BiochemBiophysResCommun398(1):86-91,2010.

4. MaekawaT,TabetaK,Kajita-OkuiK,TakahashiN,HondaT,NakajimaTandYamazakiK.IncreasedexpressionsofC-reactiveproteingeneininflamedgingivaltissuescouldbederivedfromendothelialcellsstimulatedwithinterleukin-6.ArchOralBiol201156(11):1312-1318.

5. YamazakiK,TabetaKandNakajimaT.Periodontitisasariskfactorforatherosclerosis.JOralBiosci201153(3):221–232.

6. MaekawaT,TakahashiN,TabetaK,AokiY,MiyashitaH,MiyauchiS,MiyazawaH,NakajimaTandYamazakiK.ChronicoralinfectionwithPorphyromonasgingivalisacceleratesatheromaformationbyshiftingthelipidprofile.PLoSONE6(5):e20240,2011.

7. TabetaK,TanabeN,YonezawaD,MiyashitaH,MaekawaT,TakahashiN,OkuiT,NakajimaT,YamazakiK.　ElevatedAntibodyTiterstoPorphyromonasgingivalisasaPossiblePredictorofIschemicVascularDisease.JAtherosclerThromb.201118:808-817.

8. TakahashiN,OkuiT,TabetaKandYamazakiK.EffectofInterleukin-17ontheexpressionofchemokinesingingivalepithelialcells.EurJOralSci.2011119:339–344.

9. MiyazawaH,HondaT,MiyauchiS,DomonH,OkuiT,NakajimaT,TabetaK,YamazakiK.ElevatedserumPCSK9levelsareassociatedwithperiodontalinfectionbutdonotcorrelatewithLDLcholesterollevel.ClinChimActa.2012413:154-159.

10.NakajimaT,OkuiT,MiyauchiS,HondaT,ShimadaY,ItoH,AkazawaK,YamazakiK.Theeffectsofsystemicsitafloxacinonperiodontalinfectioncontrolinelderlypatients.Gerodontology.　29(2):　e1024-e1032,2012.

11.MiyauchiS,MaekawaT,AokiY,MiyazawaH,TabetaK,NakajimaT,YamazakiK.OralinfectionwithPorphyromonasgingivalisandsystemiccytokineprofileinC57BL/6.KOR-ApoEshlmice.JPeriodont.Res.J.PeriodontRes47(3):402-408,2012.

12.MiyashitaH,HondaT,MaekawaT,TakahashiN,AokiY,NakajimaT,TabetaK,YamazakiK.Relationshipbetween

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serumantibodytiterstoPorphyromonasgingivalisandhs-CRPlevelsasinflammatorymarkersofperiodontitis.ArchsoralBiol.57(6):820-829,2012.

13.HondaT,TakahashiN,MiyauchiS,YamazakiK.PorphyromonasgingivalislipopolysaccharideinducesmiR-146awithoutalteringtheproductionofinflammatorycytokines.BiochemBiophysResCommun.420(4):918-925,2012.

14.OkuiT,AokiY,ItoH,HondaT,YamazakiK.ThepresenceofIL-17+/FOXP3+double-positivecellsinperiodontitis.JDentRes91(6):574-579,2012.

Kazuhisa Yamazaki

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Paradigm shift of orhthognathic surgery in diagnosis, simulation, and guided surgery

Tetsu Takahashi, D.D.S., Ph.D.

DivisionofOralandMaxillofacialSurgery,DepartmentofOralMedicineandSurgery,TohokuUniversityGraduateSchoolofDentistry

Thetraditionalplanningfororthognathicsurgeryusingtracinganddentalplastermodelshasremainedmostlyunchangedoverthepast50years.TheypresentsignificantlimitationsandareofteninadequateforthetreatmentofpatientswithcomplexCMFdeformities.Mytopicis3Dsurgicalsimulationfororthognathicsurgerybasedontheocclusalrelationshiptopredictsurgicaloutcomes.

BeforetakingCTscanning,impressionofthebiteandupperandlowerdentalarcheswastakenusingspecialimpressiontrayandsiliconimpressionmaterial.3-DvirtualskullmodelwithdetaileddentalocclusalandintercuspidationdatewascreatedbytripleCTscanprocedure.FirstthepatientwasverticallyscannedwithwaxbitewaferinplaceinanaturalseatedpositionusingstandardizedCTscanningprotocol.Second,thetrayandimpressionmaterialwasplacedinthepatient'smouthinthecorrectposition,andthepatientwasscannedwithasmallerfieldofviewcenteredontheocclusalplane.Finally,thespecialtrayandimpressionmaterialwasscannedmorepreciselyusinghigh-resolutionstandardizedCTscanningprotocol.ThesethreescanningdateswereinstalledtoMaxilimsoftware(Ver.2.2.2,MedicimNV,Mechelen,Belgium).Acquiringthe3Dintegratedaugmentedskullmodelwithdentition,3Dcephalometricanalysis,virtualosteotomyandsegmentationofeachbonysegmentwereundergone.Thesurgicalsimulationwasthenperformedatthepositionoffinalocclusionbyuseofvirtualelasticsbetweenupperandlowerteeth.

Nextstepfromthesimulation,weneedsomeintraoperativeguidestoacquiretheactualresultssameassimulatedresults.Therearetwopossibilitiestomakesuchguide,oneistemplatetosetontheosteotomygaptoindicatetheamountofmovementandanotherissurgicalsplintthatmadeasanintermediatesplintsameasconventionalmodelsurgery.Wehaveused3Dvirtualsurgicalsplintsmadefromatransparentpolycarbonatematerial(TecanatPolycarbonate,EisignerIndustries,US)processedusingcomputeter-aideddesignandcomputer-aidedmanufacturingtechniquesduringtheactualsurgery.

3Dvirtualorthognathicsurgeryplanninghaspowerfulpotentialasacommunicationtoolbecauseitoffersthepossibilitytovisualizeanintegratedtreatmentplanofthepatientasasinglevirtualanatomicmodelincludingthehardandsofttissueandteeth.Furthermore,thesurgicalguideshelpsurgeonstoindicateappropriate3Dlocationofmaxillarysegmentduringbimaxillarysurgery.However,tomaketheparadigmshiftfromconventionalplanningto3Dvirtualplanning,someproblemssuchastimeconsuming,costs,irradiationandqualityofcarehavetobeovercomenearfuture.

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Tetsu Takahashi

CURRICULUM VITAE

Education

1977-1983 TohokuUniversitySchoolofDentistry, SendaiJapan(D.D.S.)1983-1987 PostgraduatecourseofTohoku UniversitySchoolofDentistry,Microbiologyand OralSurgery(Ph.D.)Position

1990-1994 AssistantProfessor,DepartmentofOraland MaxillofacialSurgeryII,TohokuUniversitySchool ofDentistry,Sendai,Japan.1994-1995 AssistantProfessor,DivisionofDentistryandOral Surgery,AkitaUniversitySchoolofMedicine, Akita,Japan.Lecturer,DivisionofDentistryand OralSurgery,AkitaUniversitySchoolofMedicine, Akita,Japan. Professor,SecondDepartmentofOraland MaxillofacialSurgery,KyushuDentalCollege2012 ProfessorandHead, DivisionofOralandMaxillofacialSurgery, DepartmentofOralMedicineandSurgery, TohokuUniversitySchoolofDentistry2012 ProjectProfessor,KyushuDentalCollege VisitingProfessorandLecturer DepartmentofDentistryandOralSurgery, KanazawaMedicialUniversity KyushuUniversitySchoolofDentistry NagasakiUniversitySchoolofDentistry TokyoDentalCollege NohonUniversityMatsudoSchoolofDentistry

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Recent Paradigm Change in Three-Dimensional Imaging and CAD-CAM Technology for Virtual Orthodontic Treatment and Orthognathic Surgery

Seung - Hak Baek, D.D.S., M.S.D., Ph.D.

Dept.ofOrthodontics,SchoolofDentistry,SeoulNationalUniversity

Currentrapidchangeofparadigminthediagnosisandtreatmentforpatientswithmalocclusion

andfacialdeformitygiveanewhorizontotheorthodontictreatmentandorthognathicsurgery

intermsofefficiencyandeffectiveness.

Thispresentationwillgiveyoutheup-to-dateinformationof3D-Digitalprocesseswhich

arecurrentlybeingusedinthediagnosisandtreatmentplanning,andrealtreatmentinthe

orthodontictreatmentandorthognathicsurgeryforbothclinicalpracticeandresearch.

ThepurposesofthispresentationaretodiscussaboutthedataacquisitionfromCT,intra-oral

scanning,andsurfacescanning,thedatamanipulationincludingvirtualsegmentationofteeth,

virtualdiagnosticandfinalset-upofthemodels,virtualbracketpositioningandjigfabrication,

virtualorthognathicsurgery,andvirtualfabricationofsurgicalwafers,andtheappliance

fabricationanddeliveryforindirectbondingjigwithcustomizedbase,andsurgicalwafersusing

CAD-CAMandSLAtechnology.

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Seung-Hak Baek

CURRICULUM VITAE

Education

1. CollegeofDentistry,SeoulNationalUniversity,graduatedFebruary,1988,withthedegreeofD.D.S..

2. GraduateSchool,SeoulNationalUniversity,graduatedFebruary,1991,obtainedanM.S.D.(specializedinOrthodontics)forathesisentitled:"AsofttissueanalysisonfacialestheticsofKoreanyoungadults"

3. GraduateSchool,SeoulNationalUniversity,graduatedFebruary,1997,receivedaPh.D.(specializedinOrthodontics)forathesisentitled:"Astudyonthedistributionofseveralgrowthfactorsintheartificiallycreatedcleftlipwoundhealingofrabbitfetuses"

Position

2003–present DirectorofAcademics,SecretaryGeneral,Vice President,KoreanCleftLipandPalate Association2003–present Member.EditorialReviewBoard,Angle Orthodontist2004–present DirectorofEducation,DirectorofScientific Affairs,DirectorofPlanning,SecretaryGeneral, Director,KoreanAssociationofOrthodontists2004–present DirectorofPRandCRM,DirectorofEducation andResearch,DirectorofPlanningandBudget, SeoulNationalUniversityDentalHospital2005-2007 AssistantDean,SchoolofDentistry,Seoul NationalUniversity.2005–present Member.EditorialReviewBoard.American JournalofOrthodonticsandDentofacial orthopedics.2006–present DirectorandHeadCoach,SeoulNational UniversityRowingTeam2007-2010 Member,CommitteeofDentalCareEvaluationin MinistryofHealthandWelfare,Korea2009–present Chair,Dept.ofOrthodontics,SchoolofDentistry, SeoulNationalUniversity2010-presentFellowoftheInternationalCollegeofDentists2010–present MemberoftheGeneralAssembly,Korean AssociationofOrthodontists2011–present Member,CommissionoftheMinistryofPatriots andVeteransAffairs,Korea

Award and Honors

1. receivedasummacumscholarshipfromSeoulNationalUniversityin1986,1987

2. graduatedassummacumlaudeinSeoulNationalUniversityinFeb1988

3. TheprizeofPresidentofSeoulNationalUniversity,February,1988

4. TheprizeofPresidentofKoreanAssociationofOrthodontists,September1997

5. The10thBeomhoawardforYoungScientificResearcher(KoreandivisionofIADR),Jan24,1998.

6. UnilevertravelawardfromIADR1999,Vancouver,Canada

7. Awardof2007Year’sBook,NaturalScience,TheNationalAcademyofSciences,RepublicofKorea.“BaekSH,NahnDS.NewParadigmofCraniofacialDistractionOsteogenesis.JeeSungPub.Co.Seoul,Korea,2006.”

8. The5thYeonSongDentalAward.KoreanAcademyofDentalScience.Feb22,2009

9. CDABOCaseReportoftheYearAward,AAOmeeting.Boston,May2,2009

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Clinical and biomechanical considerations for correction of the dento-facial deformities

Young - Chel Park, D.D.S., Ph.D.

Dept.ofOrthodonticsYonseiUniversitySeoul,Korea

Sofar,theconventionalorthognathicsurgeryhasbeenwidelyusedtotreatthedentofacial

deformitypatient.However,someproblemswerefoundsuchaslimitedamountofmovement

intheskeletaltissue,highrecurrencerateanddifficultytoachievethefunctionalandesthetic

balance.Tominimizethelimitationandsideeffectsoftheorthognathicsurgery,orthopedic

interventionhasbeenwidelyusedforthetreatmentofdento-facialdeformities.Asaresult,

orthopedicinterventionsuchasdistractionosteogenesisandrapidmaxillaryexpansionhas

becameanalternativeoptionfortreatmentofhypoplasiainthepatientswithdento-facial

deformity.

Biologicandbiomechanicalbackgroundofdistractionosteogenesisforthetreatmentof

maxillaryhypoplasiaincleftlipandpalatepatientandinthehemifacialmicrosomiapatient

willbediscussedwiththeclinicalcases.Rapidmaxillaryexpansion(RME)hasbeenwidely

usedtocorrecttheverticalandtransversedeficiencyofthemaxillainthegrowingpatients.It

ispossibletoextendtheindicationofageandtherangeofmaxillaryexpansionbyusingthe

surgicallyassistedRMEandtheminiscrewassistedRME.Thecharacteristicsofsurgically

assistedRMEandtheminiscrewassistedRMEwillalsobediscussedwiththetreatedcases

andrelatedresearches.

Ifthepatientwithdento-facialdeformitywastreatedunderaccuratediagnosisandtreatment

planningwithaproperbiologicandbiomechanicalprinciples,accompaniedwithovercorrection

andlongtermretention,itwouldbepossibletoimprovethefunctionalandestheticbalance

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Young-Chel Park

CURRICULUM VITAE

Education

1975 DoctorofDentalSurgery(DDS),Yonsei University,Seoul/Korea1978 SpecialistinOrthodontics,YonseiUniversity, Seoul/Korea1984 DoctorofPhilosophy(PhD),Graduateschool,Yonsei University1984-1985 VisitingAssistantProfessor,Dept.ofOrthodontics UniversityofConnecticut,U.S.A.1998-1999 VisitingProfessor,Dept.ofOrthodontics UniversityofBritishColumbia,Vancouber, CANADA1992-2002 ProfessorandChairman,Dept.ofOrthodontics, CollegeofDentistry,YonseiUniversity2002-2004 Director,DentalHospital,YonseiUniversity2004-2008 Dean,CollegeofDentistry,YonseiUniversity, Seoul,KOREA1981-present Professor,Dept.ofOrthodontics,Collegeof Dentistry,YonseiUniversity,Seoul,KoreaPosition

1986-1990 EditorinChief,KoreanJournalofOrthodontists,1986-present InternationalMember,AmericanAssociationof Orthodontists1993-present Director,TheKoreanadultorthodonticresearch institute1994-1995 Chairman,OrganizingCommittee The2ndAsianPacificOrthodonticCongress1996 MemberofScientificCommittee,VIInternational SymposiumonDentofacialDevelopmentand Function(Athens-Greece)1996-present Member,WorldFederationofOrthodontists2000-2002 President,KoreanAssociationofOrthodontists2002 Chairman,The1stAsianImplant-Orthodontic Conference2004-present Member,EditorialReviewBoard,,Angle Orthodontists2005-present Member,EditorialReviewBoard,American JournalofOrthodonticsandDentofacial Orthopedics2007-2008 President,Dean'sCounsiloftheKoreanDental College2008 Chairman,OrganizingCommittee,The1stworld ImplantOrthodonticConferenceandthe7th AsianImplantOrthodonticConference2009-present President,WorldImplantOrthodonticAssociation2010-present President,Koreanassociationoforthodontic professors.

Publications

AngleOrthod,ObstructiveSleepApneaPatientswiththe1.OralApplianceExperiencePharyngealSizeandShapeChangesinThreeDimensions,75(1):15-22,SHKyung,YCPark,EKPae,2005JournalofclinicalOrthodontic,ExtractionSpaceClosure2.withVacuum-FormedSplintsandMiniscrewAnchorage,39(2):76-79,YCPark,JSLee,DHKim,2005JournalofclinicalOrthodontic,BondingOrthodontic3.AttachmentstoMiniscrewHeads,JCO39(6):348-353,SHKyung,HWChoi,KHKim,YCPark,2005TheKoreanJournalofOrthodontics,Anatomical4.characteristicsofthemidpalatalsutureareaforminiscrewimplantationusingCTimage35(1):35-42,YCPark,JSLee,DHKim,2005J.ofYonseiClinicalOrthod,TreatmentofskeletalclassII5.openbitewithminiscrewimplants12:65-72,YCPark,CYJoo,2005ShinheungInternational,Currentadultorthodontic6.treatmentVol.IIIorthodontictreatmentbyusingminiimplant,YCPark,JKKim,JSLee,2005DaehannaraePublishing,Clinicalbiomechanicsand7.estheticstrategy,YCPark,HSHwang,KCChoi,SJSung,2006AmJOrthodDentotofacialOrthop.Soft-tissueandcortical-8.bonethicknessatorthodonticimplantsites,130(3):177-182,HJKim,HSYun,HDPark,DHKim,YCPark,2006J.Thai.Assoc.Orthod.En-masseDistalizationofUpper9.DentitionforthecorrectionofClassIIUsingDualOrthodonticMiniscrews,5:33-38,KJLee,YCPark,2006TheKoreanJournalofOrthodontics,Frictionalresistance10.ofdifferentceramicbracketsandtheirrelationshiptothesecondorderangulationbetweenbracketslotandwire,36(3):207-217,YJChoi,YCPark,2006TheKoreanJournalofOrthodontics,Craniofacial11.morphologicalterationinducedbybone-targetedmutantsofFGFR2causingApertandCrouzonsyndrome.36(4):284-294,KJLee,HDNa,STEPHEN,YCPark,HSBaik,TMYoon,JWSong,2006Quintessencebookco.,ApplicationsofOrthodonticMini-12.implants,JSLee,JKKim,YCPark,RobertL,Vanarsdall,Jr,2007AngleOrthodontist,TreatmentofClassIIProtrusionwith13.SevereCrowdingUsingIndirectMiniscrewAnchorage,77(6):1109-1118,NCChoi,YCPark,HALee,KJLee,2007JournalofClinicalOrthodontic,UprightingMandibular14.SecondMolarswithDirectMiniscrewAnchorage,41(10):277-285,KJLee,YCPark,WSHwang,UHSeong,2007Am.J.Orthod.DentotofacialOrthop,Estheticsegmental15.retractionofmaxillaryanteriorteethwithapalatalapplianceandorthodonticmini-implant,131:537-544,YCPark,YJChoi,NCChoi,JSLee,2007TheKoreanJournalofOrthodontics,Changesinlipand16.

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periornlsofttissueafterbracketremoval,37(2)125-136,JSLee,KCChoy,YCPark,KHKim,2007TheKoreanJournalofOrthodontics,Treatmentand17.posttreatmentchangesfollowingintrusiononmaxillaryposteriorteethwithminiscrewimplantsforopenbitecorrection.38(1):31-40,HALee,YCPark,2008TheKoreanJournalofOrthodontics,Labialandbuccal18.surfacecontoursofKoreannormalocclusioninathree-dimensionaldigitalmodel,38(2):95-103,SWSong,JYCho,JSChoi,YCPark,JHChae,2008TheKoreanJournalofOrthodontics,Theeffectofloading19.timeonthestabilityofmini-implant,38(3):149-158,SYLee,JYCha,TMYoon,YCPark,2008AngleOrthodontist,NasalChangesafterSurgical20.CorrectionofSkeletelClassⅢMalocclusioninKoreans,78(3):427-432,CJChung,YBLee,KHPark,SHPark,YCPark,KHoKim,2008AngleOrthodontist,OpenBiteCorrectionbyIntrusionof21.PosteriorTeethwithMiniscrew,78(4):699-710,YCPark,HALee,NCChoi,DHKim,2008Int'lJofOral&maxilofacialimplant,Influenceof22.theLengthoftheLoadingPeriodAfterPlacementofOrthodonticMini-implantsonChangesinBoneHistomorphology:MicrocomputedTomographicandHistologicAnalysis.24:842-849,JYCha,JKLim,,JWSong,DaisukeSato,MakotoKenmotsu,Takashilnoue,YCPark,2009AmJOrthodDentofacialOrtho,Restotationofanalveolar23.bonedefectcausedbyanankylosedmandibularmolarbyrootmovementoftheadjacenttoothwithminisrewimplants,136:440-449,KJLee,EJ,HSYu,YCPark,2009AmJOrthodDentofacialOrtho,Computedtomographic24.analysisoftooth-bearingalveolarbonefororthodonticminiscrewplacement,135(4):486-494,KJLee,EJ,KDKim,JSLee,YCPark,HSYu.,2009AmericanJournalOfOrthodonticsAndDentofacial25.Orthopedics,Combineduseofminiscrewsandclearappliancesforthetreatmentofbialveolarprotrusionwithoutconventionalbrackets135:671-681,NCChoi,YCPark,YMJo,KJLee,2009J.YonseiClinicalOrthod,LingualtreatmentofclassI26.malocclusion,16:103-112,JHChae,YCPark,2009NON-EXtractionFACTORS,98.5%NonextractionTherapy27.usingCoordinatedArchDevelopment,Chapter2-7,KJLee,YCPark,2010AmericanJournalOfOrthodonticsAndDentofacial28.Orthopedics,Long-termstabilityofanterioropen-bitetreatmentbyintrusionofmaxillaryposteriorteeth.138(1):396.e1-396.e9,MSBeak,YJChoi,HSYu,KJLee,JinnyKwak,YCPark,2010J.YonseiClinicalOrthod,CasereportofclassI29.malocclusiontreatmentwithunilateralmolarcross,18:57-64,JJPark,,YCPark,2011AngleOrthodontist,Radiographicevaluationsofmolar30.

intrusionandchangeswithorwithoutretentioninrats,81:389-396,YJChoi,KHKim,KJLee,CJChung,YCPark,2011TheKoreanJournalofOrthodontics,Finiteelement31.analysisofeffectivenessofleverarminlingualslidingmechanics.41(5):324-336,KHKim,KJLee,JYCha,YCPark,2011TheKoreanJournalofOrthodontics,Threedimensional32.finiteelementanalysisofcontinuousandsegmentedarcheswithuseoforthodonticminiscrews,41(4):237-254KHKim,KJLee,JYCha,YCPark,201133.AmericanJournalofOrthodonticsandDentofacial34.Orthopedics,Displacementpatternofthemaxillaryarchdependingonminiscrewpositioninslidingmechanics140(2):224-232,KJLee,YCPark,CJHwang,THChoi,2011AmJOrthodDentofacialOrthop,Totaldistalizationof35.themaxillaryarchinapatientwithskeletalClassIImalocclusion,139(6):823-833,YJChoi,SJLee,JYCha,YCPark,2011

Young-Chel Park

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Orthognathic Surgery :The Considerations for its Accuracy and Safety

Kiyoshi Harada, D.D.S., Ph.D.

MaxillofacialSurgerySection,GraduateSchoolofMedicalandDentalSciences

Noworthognathicsurgeryisoneofthemostcommonsurgicalmethodsforthetreatmentofdento-facialdeformitypatients.Thoughtherearemanytechniquefororthognathicsurgery,sagittalsplittingofthemandibularramusandLeFortⅠosteotomyofthemaxillaarethemostpopular.Sincethesepopularorthognathicsurgerieshavebeenwelltrainedbyoralsurgeons,fewmajortroubleshavebeenreportedduringsurgeryrecently.However,resultsoftheorthognathicsurgeryshouldbebasedontheimprovementofocclusaldisharmony.Thepostoperativeocclusalconditiondependsonaccuracyofthesurgicalmovementonthejawbones.Inaddition,asasurgicalbasis,thetechniquesforaccuratebonemovementshouldbefreefromunexpectedbleedingorjawbonefracture.Sinceorthognathicsurgeryisbecomingacommontreatmentmethodinthefieldoforalandmaxillofacialsurgery,safetymustbeguaranteedduringsurgery.Inthislecture,severaloriginaltechniquesareintroducedforaccurateandsafemovementofjawboneduringorthognathicsurgery.

Inthesagittalsplittingofthemandibularramus,thebilateralmandibularramiaresplitintotheproximalanddistalsegments.Thedistalsegmentismovedposteriororanteriortoimprovetheocclusaldisharmony.However,theproximalsegmentmustbemaintainedinitsoriginalpositionduetothepresenceofcondyle.Improperpositioningoftheproximalsegment,namely,condylecancausevariousproblemsoftemporomandibularjointandinstabilityofthepostoperativeocclusion.Therefore,itisconsideredtobebetterthatthepre-splittingpositionoftheproximalsegmentshouldberecordedusingadevice.Eventhoughbeginnersoftheorthognathicsurgeryperformthesagittalsplittingofthemandibularramus,luxationofthetemporomandibularjointcanbepreventedusingthisdeviceduringsurgery.

Inthemaxillaryosteotomy,accurateupwardimpactionisdifficultbecausethereareimportantbloodvesselsnourishingthemaxillainitsposteriorportion.Thoughsomeoralsurgeonsperformupwardhammeringofthemaxillaforitsupwardmovement,it’sverydanger.Thepresenceofinferiorconchaand,inthesimilarsituation,nasal-intubatedendotrachealtubealsointerferesduringupwardmovementofthemaxillarysegment.Tosolvetheseproblemsofupwardmovementofthemaxilla,additionalosteotomytoLeFortⅠorapplicationofresinreplicaisperformedduringsurgery.

Thesetechniqueshavenotonlyadvantages,butalsosomedisadvantages.Ihopetheaccuracyandsafetyoforthognathicsurgerywillbediscussedthroughthislecturetoincreasethequalityoflivesofthepatientsundergoingorthognathicsurgery.

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Kiyoshi Harada

CURRICULUM VITAE

Education

1985 GraduatedfromTokyoMedicalandDentalUniversity,FacultyofDentistry.

1985 EnteredtheGraduateSchoolofTokyoMedicalandDentalUniversity,FacultyofDentistry,andjoinedthe2ndDepartmentofOralandMaxillofacialSurgeryasaGraduateStudent.

1989 GraduatedfromtheGraduateSchoolofTokyoMedicalandDentalUniversity,FacultyofDentistry,andAppointedtoaClinicalFellowofthe2ndDepartmentofOralandMaxillofacialSurgery.

Position

AppointedtoaClinicalFellowin1989.1.TransferredtotheDepartmentofPlasticSurgery,Faculty2.ofMedicine,KitasatoUniversityasanAssistantProfessor(Instructor)in1990.Returnedtothe23. ndDepartmentofOralandMaxillofacialSurgery,FacultyofDentistry,TokyoMedicalandDentalUniversityasanAssistantProfessor(Instructor)in1992.AppointedtoanAssistantProfessor(Lecturer)in2003.4.AppointedtoanAssociateProfessorin2004.5.AppointedtoaProfessorandChairmanoftheDepartment6.ofOralandMaxillofacialSurgery,UniversityHospital,FacultyofMedicine,UniversityofYamanashiin2006.AppointedtoaProfessoroftheDepartmentofOral7.andMaxillofacialSurgery,DivisionofMedicine,InterdisciplinaryGraduateSchoolofMedicineandEngineering,UniversityofYamanashiin2008.AppointedtoaProfessoroftheSectionofMaxillofacial8.Surgery,DepartmentofMaxillofacial/NeckReconstruction,GraduateSchoolofMedicalandDentalSciences,TokyoMedicalandDentalUniversityin2012,andservinginthatpositionuptothisdate.

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東京医科歯科大学

http://www.tmd.ac.jp/cmn/gcoe/index.html

第7回グローバルCOE国際シンポジウム

Molecular Science in Oral-Systemic Medicine ~Autumn Seminar~