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Car$lago Ar$cular y Osteoartrosis
Asesor: Dr. Med. Eduardo Álvarez
Tomás Alejandro Ramos Sánchez R3
CarDlago Ar$cular
Tejido elás$co avascular, aneural y alinfá$co que recubre las ar$culaciones diartrodiales del
esqueleto
CarDlago Ar$cular
• Función – Facilita el deslizamiento y lubricación ar$cular – Disminuye la fricción y ayuda a la movilidad sin dolor
– Absorbe los trauma$smos mecánicos – Distribuye las cargas sobre el hueso subyacente
CarDlago Ar$cular • Condrocitos • Matriz extracelular
– Colágeno – Proteoglicanos – Proteínas no colagenicas
Articular cartilage contains two major classes of pro-teoglycans: large aggregating molecules or aggrecans (Fig-ure 4) and smaller proteoglycans including decorin (dEco-RIn), biglycan, and fibromodulin. Because it may have aglycosaminoglycan component, type IX collagen is alsoconsidered a proteoglycan. Aggrecans have large numbersof chondroitin sulfate and keratan sulfate chains attachedto a protein core filament (Figure 5). Decorin has one der-matan sulfate chain, biglycan has two dermatan sulfatechains, and fibromodulin has several keratan sulfatechains. Aggrecan molecules fill most of the interfibrillarspace of the cartilage matrix. They contribute about 90%of the total cartilage matrix proteoglycan mass, whereaslarge nonaggregating proteoglycans contribute 10% or lessand small nonaggregating proteoglycans contribute about3%.
In the articular cartilage matrix, most aggrecans (Fig-ure 6) noncovalently associate with hyaluronic acid (hy-aluronan) and link proteins, small noncollagenous pro-teins, to form proteoglycan aggregates (Figure 4). Theselarge molecules have a central hyaluronan backbone thatcan vary in length from several hundred nanometers tomore than 10,000 nanometers. Large aggregates may havemore than 300 associated aggrecan molecules. Link pro-teins stabilize the association between monomers and hy-aluronic acid. Aggregate formation helps anchor pro-teoglycans within the matrix, preventing theirdisplacement during deformation of the tissue, and helpsorganize and stabilize the relationship between proteogly-cans and the collagen meshwork.
The small nonaggregating proteoglycans have shorterprotein cores than aggrecan molecules, and unlike aggre-cans they do not fill a large volume of the tissue or con-
tribute directly to the mechanical behavior of the tissue.Instead they bind to other macromolecules and probablyinfluence cell function. Decorin and fibromodulin bindwith type II collagen and may have a role in organizingand stabilizing the type II collagen meshwork, and bigly-can may interact with type VI collagen. The small pro-teoglycans also can bind transforming growth factor βand may limit healing of cartilage and alter degradativeenzyme production.
N o ncolla g e n o us Pro t eins a n d Glyco pro t einsA wide variety of noncollagenous proteins and glycopro-teins exist within normal articular cartilage and appear toconsist primarily of protein and a few attached monosac-charides and oligosaccharides. Some of these appear tohelp organize and maintain the macromolecular structureof the matrix. Anchorin CII, a collagen-binding chondro-cyte surface protein, may help “anchor” chondrocytes tothe matrix collagen fibrils. Cartilage oligomeric protein(COMP), an acidic protein, is concentrated primarilywithin the chondrocyte territorial matrix and appears tobe present only within cartilage and have the capacity tobind to chondrocytes. Fibronectin and tenascin, noncol-lagenous matrix proteins that are found in a variety of tis-sues, have also been identified within cartilage but thusfar their functions are not well understood.
Zones of Articular CartilageThe morphologic changes in chondrocytes and matrixfrom the articular surface to the subchondral bone makeit possible to identify four zones, or layers: the superficialzone, the transitional zone, the radial zone, and the zone
Figure 6 A, Electro n micro gra p h sh o w in g t h e articular cartila g e m a trix co m p art m e n ts o f t h e m e dial f e m oral co n dyle o f a n8-m o n t h-old ra b bit . A rro w h e a ds in dica t e p ericellular m a trix, * in dica t es t errit orial m a trix. Bar = 3 n m . B, A hig h er m a g nifica tio nelectro n micro gra p h sh o w in g t h e sa m e m a trix co m p art m e n ts a n d t h e rela tio nship b e t w e e n t h e cell m e m bra n e a n d t h e p ericellularm a trix. Bar = 1 n m . N o tice t h e sh ort-cell processes t h a t ext e n d t hro u g h t h e p ericellular m a trix. (Re pro d uce d fro m Buck w alt er JA ,H u n zik er EB, Rose n b erg LC, e t al: A rticular cartila g e: Co m p osit io n a n d struct ure , in W o o SL, Buck w alt er JA (e ds): Injury a n d Re p air o ft h e M usculosk ele t al So f t Tissu es. Park Rid g e , IL, A m erica n Aca d e my o f O rt h o p a e dic Surg e o ns, 1988, p p 405-425.)
Chapter 9 Articular Cartilage and Osteoarthritis
165American Academy of Orthopaedic Surgeons | Orthopaedic Basic Science, ed 3
Condrocitos • Células especializadas, derivan de las células madre
pluripotenciales del mesénquima • Representan el 1% del volumen total. • Difirieren en forma, tamaño y ac$vidad metabólica en las
diferentes capas. • ReDculo endoplasmico y aparato de Golgi • La edad altera su funcionamiento
tial for cartilage resiliency and joint lubrication or in theconcentrations of collagen and proteoglycans. It is clear,however, that the chondrocytes are in large measure re-sponsible for the maintenance and structural competence
of these materials and for allowing them to carry out theirrequired activities and functions. The chondrocytes areresponsible for producing and replacing appropriateamounts of macromolecules and assembling them into ahighly ordered macromolecular framework. To accom-plish these activities, the cells must sense changes in thematrix composition caused by degradation of macromol-ecules and the mechanical demands placed on the articu-lar surface, and then respond by synthesizing appropriatetypes and amounts of macromolecules.
Aging profoundly alters chondrocyte function. Withaging, the capacity of the cells to synthesize some types ofproteoglycans, their proliferative capacity, and their re-sponse to anabolic stimuli (including growth factors) de-creases. These changes may limit the ability of the cells tomaintain and restore the tissue and thereby contribute tothe development and progression of articular cartilage de-generation.
Extracellular M a trixThe articular cartilage matrix consists of two compo-nents: the tissue fluid and the framework of structuralmacromolecules that give the tissue its form and stability.The interaction of the tissue fluid and the macromolecu-lar framework give the tissue its mechanical properties ofstiffness and resilience. Water contributes up to 80% of
Figure 1 A rticular cartila g e fro m t h e m e dial f e m oral co n dyleo f a n 8-m o n t h-old ra b bit . Th e tissu e is org a niz e d in t o f o ur lay-ers or z o n es: t h e su p erficial z o n e (S), t h e tra nsit io n al z o n e (T),t h e mid dle (ra dial or d e e p) z o n e (M), a n d t h e calcif ie d cartila g ez o n e (C). Bar = 50 n m . (Re pro d uce d fro m Buck w alt er JA , H u n-zik er EB, Rose n b erg LC, e t al: A rticular cartila g e: Co m p osit io na n d struct ure , in W o o SL, Buck w alt er JA (e ds): Injury a n d Re p airo f t h e M usculosk ele t al So f t Tissu es. Park Rid g e , IL, A m erica nAca d e my o f O rt h o p a e dic Surg e o ns, 1988, p p 405-425.)
Figure 2 Electro n micro gra p hs sh o w in g t h e su p erficial z o n e (A), tra nsit io n al z o n e (B), mid dle (ra dial or d e e p) z o n e (C), a n d calci-f ie d cartila g e z o n e (D) o f m a t ure articular cartila g e ch o n drocyt es fro m t h e m e dial f e m oral co n dyle o f a ra b bit . N = n ucle us, G =glyco g e n , IF = in t erm e dia t e fila m e n ts, M M = min eraliz e d m a trix, U M = u n min eraliz e d m a trix, b ar = 3 n m . (Re pro d uce d fro m Buck-w alt er JA , H u n zik er EB, Rose n b erg LC, e t al: A rticular cartila g e: Co m p osit io n a n d struct ure , in W o o SL, Buck w alt er JA (e ds): Injury a n dRe p air o f t h e M usculosk ele t al So f t Tissu es. Park Rid g e , IL, A m erica n Aca d e my o f O rt h o p a e dic Surg e o ns, 1988, p p 405-425.)
162
Section 2 Physiology of Musculoskeletal Tissues
Orthopaedic Basic Science, ed 3 | A merican Academy of Orthopaedic Surgeons
Condrocitos • Función
– Producen y man$ene la matriz extracelular. – Responden a cambios en la composición de la matriz extracelular
• Degradación de macromoléculas • Demandas mecánicas sobre la superficie ar$cular
• Respuesta – Sinte$zan macromoléculas
• (colágeno, proteoglicanos)
Matriz extracelular • Agua
– 70% del peso del carDlago ar$cular
• Macromoléculas estructurales – Da al tejido su forma y estabilidad – 30% del peso del carDlago ar$cular
• Colágeno 60% • Proteoglicanos 25% a 35% • Proteínas no colagenicas 15% a 20%
Rigidez y Resistencia
Matriz Extracelular • Función
– Rigidez y resistencia del tejido – Protege las células del daño causado por el uso. – Flexibilidad y Lubricación del tejido
• Proteoglicanos de cadena larga (Agrecanos) – Limita el ingreso y egreso de moléculas al liquido sinovial.
Agrecanos • Gran numero de cargas nega$vas
– Incrementa la osmolaridad del tejido – Atrae iones de carga posi$va
• Sodio – Repele iones de carga nega$va
• Cloro
Colágeno • La mas común $po II (90% a 95%)
– VI, IX, X, XI • Se distribuye uniformemente a través de las diferentes zonas excepto zona superficial
• Colágeno $po IX une la red fibrilar con los proteoglicanos
• Colágeno $pos VI une los condrocitos con la matriz extracelular
Colágeno • II, IX XI forman la red fibrilar que se observa en el microscopio electrónico
the weight of articular cartilage and the interaction of wa-ter with the matrix macromolecules significantly influ-ences the mechanical properties of the tissue. Some of thewater is in the form of a gel and thus with pressure canmove freely in and out of the tissue. With pressure on thecartilage the water may move out of the tissue and form arelationship with the cartilage surface, which then servesas the lubrication system for cartilage movement on carti-lage. The volume, concentration, and behavior within thetissue depends primarily on its interaction with the struc-tural macromolecules: in particular, the large aggregatingproteoglycans that help maintain the fluid within the ma-trix and the fluid electrolyte concentrations. Because thesemacromolecules have large numbers of negative chargesthat attract positively charged ions and repel negativelycharged ions, they increase the concentration of positiveions such as sodium and decrease the concentration ofnegative ions such as chloride. The increase in total inor-ganic ion concentration increases the tissue osmolarity.
Struct ural M acro m oleculesThe cartilage structural macromolecules, collagens, pro-teoglycans, and noncollagenous proteins contribute 20%to 40% of the wet weight of the tissue. The three classes of
macromolecules differ in their concentrations within thetissue and in their contributions to the tissue properties.Collagens contribute about 60% of the dry weight ofcartilage, proteoglycans contribute 25% to 35%, and thenoncollagenous proteins and glycoproteins contribute15% to 20%. Collagens are distributed relatively uni-formly throughout the depth of the cartilage, except forthe collagen-rich superficial zone (“the skin” of cartilagein which the collagen fibers run parallel the surface). Thecollagen fibrillar meshwork gives cartilage its form andtensile strength and also is responsible for maintaining thephysical location of the chondrocyte. Proteoglycans andnoncollagenous proteins bind to the collagenous mesh-work or become mechanically entrapped within it, andwater fills this molecular framework. Some noncollage-nous proteins help organize and stabilize the matrix mac-romolecular framework whereas others help chondrocytesbind to the macromolecules of the matrix.
Articular cartilage, like most tissues, contains multiplegenetically distinct collagen types, the major ones beingcollagen types II, VI, IX, X and XI. Collagen types II, IXand XI form the cross-banded fibrils seen by electron mi-croscopy (Figure 3). The organization of these fibrils into atight meshwork that extends throughout the tissue pro-
Figure 3 Electro n micro gra p hs sh o w in g t h e su p erficial z o n e (A), tra nsit io n al z o n e (B), u p p er p ortio n o f t h e mid dle (ra dial or d e e p)z o n e (C), a n d lo w er p ortio n o f t h e mid dle z o n e (D) o f t h e articular cartila g e in t ert errit orial m a trix fro m t h e m e dial f e m oral co n dyleo f a n 8-m o n t h-old ra b bit . A rro ws in dica t e pro t e o glyca ns precipit a t e d w it h ru t h e niu m h exa min e trichlorid e . Bar = 0.5 n m . (Re pro-d uce d fro m Buck w alt er JA , H u n zik er EB, Rose n b erg LC, e t al: A rticular cartila g e: Co m p osit io n a n d struct ure , in W o o SL, Buck w alt erJA (e ds): Injury a n d Re p air o f t h e M usculosk ele t al So f t Tissu es. Park Rid g e , IL, A m erica n Aca d e my o f O rt h o p a e dic Surg e o ns, 1988, p p405-425.)
Chapter 9 Articular Cartilage and Osteoarthritis
163American Academy of Orthopaedic Surgeons | Orthopaedic Basic Science, ed 3
Colágeno • Función
– Forma y fuerza tensil al carDlago
– Forma una red fibrilar
– Mantener la localización bsica de los condrocitos
Proteoglicanos • Proteína + 1 ó mas cadenas de glucosaminoglicanos
• La concentración varia de acuerdo a la ar$culación, edad, daño ar$cular y enfermedad.
• Glucosaminoglicanos: disacáridos repe$dos – Acido hialuronico – Condroi$n sulfato – Keratan sulfato – Dermatan sulfato
.
vides the tensile stiffness and strength of articular cartilageand contributes to the cohesiveness of the tissue by me-chanically entrapping the large proteoglycans. The princi-pal articular cartilage collagen, type II, accounts for 90%to 95% of the cartilage collagen and forms the primary
component of the cross-banded fibrils. Type IX collagenmolecules bind covalently to the superficial layers of thecross-banded fibrils and project into the matrix wherethey also can bind covalently to other type IX collagenmolecules. Type XI collagen molecules bind covalently totype II collagen molecules and probably form part of theinterior structure of the cross-banded fibrils. The project-ing portions of type IX collagen molecules may also helpbind together the collagen fibril mesh and connect the col-lagen meshwork with proteoglycans. Type VI collagen ap-pears to form an important part of the matrix immediatelysurrounding chondrocytes and help chondrocytes attachto the matrix. The presence of type X collagen only nearthe cells of the calcified cartilage zone of articular cartilageand the hypertrophic zone of growth plate (where the lon-gitudinal cartilage septa begin to mineralize) suggests thatit has a role in cartilage mineralization.
Pro t e o glyca nsProteoglycans consist of a protein core and one ormore gly-cosaminoglycan chains (long unbranched polysaccharidechains) consisting of repeating disaccharides that contain anamino sugar. Each disaccharide unit has at least one nega-tively charged carboxylate or sulfate group, so the gly-cosaminoglycans form long strings of negative charges thatrepel one another and attract cations. Glycosaminoglycansfound in cartilage include hyaluronic acid, chondroitin sul-fate, keratan sulfate, and dermatan sulfate. The concentra-tion of these molecules varies among sites within articularcartilage and also with age, cartilage injury, and disease.
Figure 4 Tra nsmissio n electro n micro gra p h sh o w in g b ovin earticular cartila g e pro t e o glyca n a g gre g a t es fro m a calf (A) a n dst e er (B) co nsistin g o f ce n tral hyaluro n a n fila m e n ts a n d m ultiplea t t ach e d a g greca ns. A g gre g a t es fro m old er a nim als h ave sh ort-er hyaluro n a n fila m e n ts a n d f e w er a g greca ns. In a d ditio n , t h ea g greca ns are sh ort er a n d vary m ore in le n g t h . Bar = 500 n m .(Re pro d uce d w it h p ermissio n fro m Buck w alt er JA , K u e t t n er KE,Th o n ar EJ-M : A g e-rela t e d ch a n g es in articular cartila g e pro-t e o glyca ns: Electro n microsco pic st u dies. J O rt h o p Res 1985;3:251-257.)
Figure 5 A, A t o mic f orce im a g e o f a g greca n fro m f e t al b ovin e e pip hyse al cartila g e . N o t e t h a t glycosa min o glyca n ch ains projectfro m t h e ce n tral pro t ein fila m e n t o f t h e a g greca n m olecule . B, A t o mic f orce im a g e o f a g greca n fro m m a t ure b ovin e n asal cartila g e .N o t e t h a t t h e a g greca n m olecule fro m a sk ele t ally m a t ure a nim al is sh ort er a n d h as sh ort er glycosa min o glyca n ch ains. (Re pro d uce dw it h p ermissio n fro m N g L, Gro d zinsky AJ, Sa n dy JD , e t al: Struct ure a n d co n f orm a tio n o f in divid u al a g greca n m olecules a n d t h eco nstit u e n t G A G ch ains via a t o mic f orce microsco py. J Struct Biol 2003;143:242-257.)
164
Section 2 Physiology of Musculoskeletal Tissues
Orthopaedic Basic Science, ed 3 | A merican Academy of Orthopaedic Surgeons
Proteoglicanos • 2 $pos principales
– Moléculas de cadena Larga 90% • Agrecanos
– Moléculas Cortas 10% • Decorinas • Biglycano • Fibromodulina • Colágeno $po IX
Proteínas no colágenicas y glucocoproteínas
• Proteínas, monosacáridos u oligosacáridos
• Ayudan a organizar y mantener la estructura macromolecular
• Ancorina CII (ancla condrocitos a las fibras de colágeno)
CarDlago Ar$cular
• Zonas – Superficial o tangencial
– Transicional
– Zona media o radial – Zona de carDlago calcificado
tial for cartilage resiliency and joint lubrication or in theconcentrations of collagen and proteoglycans. It is clear,however, that the chondrocytes are in large measure re-sponsible for the maintenance and structural competence
of these materials and for allowing them to carry out theirrequired activities and functions. The chondrocytes areresponsible for producing and replacing appropriateamounts of macromolecules and assembling them into ahighly ordered macromolecular framework. To accom-plish these activities, the cells must sense changes in thematrix composition caused by degradation of macromol-ecules and the mechanical demands placed on the articu-lar surface, and then respond by synthesizing appropriatetypes and amounts of macromolecules.
Aging profoundly alters chondrocyte function. Withaging, the capacity of the cells to synthesize some types ofproteoglycans, their proliferative capacity, and their re-sponse to anabolic stimuli (including growth factors) de-creases. These changes may limit the ability of the cells tomaintain and restore the tissue and thereby contribute tothe development and progression of articular cartilage de-generation.
Extracellular M a trixThe articular cartilage matrix consists of two compo-nents: the tissue fluid and the framework of structuralmacromolecules that give the tissue its form and stability.The interaction of the tissue fluid and the macromolecu-lar framework give the tissue its mechanical properties ofstiffness and resilience. Water contributes up to 80% of
Figure 1 A rticular cartila g e fro m t h e m e dial f e m oral co n dyleo f a n 8-m o n t h-old ra b bit . Th e tissu e is org a niz e d in t o f o ur lay-ers or z o n es: t h e su p erficial z o n e (S), t h e tra nsit io n al z o n e (T),t h e mid dle (ra dial or d e e p) z o n e (M), a n d t h e calcif ie d cartila g ez o n e (C). Bar = 50 n m . (Re pro d uce d fro m Buck w alt er JA , H u n-zik er EB, Rose n b erg LC, e t al: A rticular cartila g e: Co m p osit io na n d struct ure , in W o o SL, Buck w alt er JA (e ds): Injury a n d Re p airo f t h e M usculosk ele t al So f t Tissu es. Park Rid g e , IL, A m erica nAca d e my o f O rt h o p a e dic Surg e o ns, 1988, p p 405-425.)
Figure 2 Electro n micro gra p hs sh o w in g t h e su p erficial z o n e (A), tra nsit io n al z o n e (B), mid dle (ra dial or d e e p) z o n e (C), a n d calci-f ie d cartila g e z o n e (D) o f m a t ure articular cartila g e ch o n drocyt es fro m t h e m e dial f e m oral co n dyle o f a ra b bit . N = n ucle us, G =glyco g e n , IF = in t erm e dia t e fila m e n ts, M M = min eraliz e d m a trix, U M = u n min eraliz e d m a trix, b ar = 3 n m . (Re pro d uce d fro m Buck-w alt er JA , H u n zik er EB, Rose n b erg LC, e t al: A rticular cartila g e: Co m p osit io n a n d struct ure , in W o o SL, Buck w alt er JA (e ds): Injury a n dRe p air o f t h e M usculosk ele t al So f t Tissu es. Park Rid g e , IL, A m erica n Aca d e my o f O rt h o p a e dic Surg e o ns, 1988, p p 405-425.)
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Section 2 Physiology of Musculoskeletal Tissues
Orthopaedic Basic Science, ed 3 | A merican Academy of Orthopaedic Surgeons
Zona Superficial o tangencial • La zona mas delgada • Fuerte y rígida • Se divide en 2 capas
– 1.-‐ fibras pequeñas, pocos polisacáridos, sin células • Lamina Splendens
– 2.-‐ Condrocitos planos de forma helicoidal y paralelos a la superficie ar$cular
– Alta concentración de colágeno y baja de proteoglicanos
– Alta concentración de agua y fibronec$na
Zona Transicional • Mayor espesor que la zona superficial • Condrocitos esferoidales • Fibras colágeno
– Mayor diámetro – No organizadas y oblicuas a la superficie
• Mayor contenido de proteoglicanos • Menos concentración de agua
tial for cartilage resiliency and joint lubrication or in theconcentrations of collagen and proteoglycans. It is clear,however, that the chondrocytes are in large measure re-sponsible for the maintenance and structural competence
of these materials and for allowing them to carry out theirrequired activities and functions. The chondrocytes areresponsible for producing and replacing appropriateamounts of macromolecules and assembling them into ahighly ordered macromolecular framework. To accom-plish these activities, the cells must sense changes in thematrix composition caused by degradation of macromol-ecules and the mechanical demands placed on the articu-lar surface, and then respond by synthesizing appropriatetypes and amounts of macromolecules.
Aging profoundly alters chondrocyte function. Withaging, the capacity of the cells to synthesize some types ofproteoglycans, their proliferative capacity, and their re-sponse to anabolic stimuli (including growth factors) de-creases. These changes may limit the ability of the cells tomaintain and restore the tissue and thereby contribute tothe development and progression of articular cartilage de-generation.
Extracellular M a trixThe articular cartilage matrix consists of two compo-nents: the tissue fluid and the framework of structuralmacromolecules that give the tissue its form and stability.The interaction of the tissue fluid and the macromolecu-lar framework give the tissue its mechanical properties ofstiffness and resilience. Water contributes up to 80% of
Figure 1 A rticular cartila g e fro m t h e m e dial f e m oral co n dyleo f a n 8-m o n t h-old ra b bit . Th e tissu e is org a niz e d in t o f o ur lay-ers or z o n es: t h e su p erficial z o n e (S), t h e tra nsit io n al z o n e (T),t h e mid dle (ra dial or d e e p) z o n e (M), a n d t h e calcif ie d cartila g ez o n e (C). Bar = 50 n m . (Re pro d uce d fro m Buck w alt er JA , H u n-zik er EB, Rose n b erg LC, e t al: A rticular cartila g e: Co m p osit io na n d struct ure , in W o o SL, Buck w alt er JA (e ds): Injury a n d Re p airo f t h e M usculosk ele t al So f t Tissu es. Park Rid g e , IL, A m erica nAca d e my o f O rt h o p a e dic Surg e o ns, 1988, p p 405-425.)
Figure 2 Electro n micro gra p hs sh o w in g t h e su p erficial z o n e (A), tra nsit io n al z o n e (B), mid dle (ra dial or d e e p) z o n e (C), a n d calci-f ie d cartila g e z o n e (D) o f m a t ure articular cartila g e ch o n drocyt es fro m t h e m e dial f e m oral co n dyle o f a ra b bit . N = n ucle us, G =glyco g e n , IF = in t erm e dia t e fila m e n ts, M M = min eraliz e d m a trix, U M = u n min eraliz e d m a trix, b ar = 3 n m . (Re pro d uce d fro m Buck-w alt er JA , H u n zik er EB, Rose n b erg LC, e t al: A rticular cartila g e: Co m p osit io n a n d struct ure , in W o o SL, Buck w alt er JA (e ds): Injury a n dRe p air o f t h e M usculosk ele t al So f t Tissu es. Park Rid g e , IL, A m erica n Aca d e my o f O rt h o p a e dic Surg e o ns, 1988, p p 405-425.)
162
Section 2 Physiology of Musculoskeletal Tissues
Orthopaedic Basic Science, ed 3 | A merican Academy of Orthopaedic Surgeons
the weight of articular cartilage and the interaction of wa-ter with the matrix macromolecules significantly influ-ences the mechanical properties of the tissue. Some of thewater is in the form of a gel and thus with pressure canmove freely in and out of the tissue. With pressure on thecartilage the water may move out of the tissue and form arelationship with the cartilage surface, which then servesas the lubrication system for cartilage movement on carti-lage. The volume, concentration, and behavior within thetissue depends primarily on its interaction with the struc-tural macromolecules: in particular, the large aggregatingproteoglycans that help maintain the fluid within the ma-trix and the fluid electrolyte concentrations. Because thesemacromolecules have large numbers of negative chargesthat attract positively charged ions and repel negativelycharged ions, they increase the concentration of positiveions such as sodium and decrease the concentration ofnegative ions such as chloride. The increase in total inor-ganic ion concentration increases the tissue osmolarity.
Struct ural M acro m oleculesThe cartilage structural macromolecules, collagens, pro-teoglycans, and noncollagenous proteins contribute 20%to 40% of the wet weight of the tissue. The three classes of
macromolecules differ in their concentrations within thetissue and in their contributions to the tissue properties.Collagens contribute about 60% of the dry weight ofcartilage, proteoglycans contribute 25% to 35%, and thenoncollagenous proteins and glycoproteins contribute15% to 20%. Collagens are distributed relatively uni-formly throughout the depth of the cartilage, except forthe collagen-rich superficial zone (“the skin” of cartilagein which the collagen fibers run parallel the surface). Thecollagen fibrillar meshwork gives cartilage its form andtensile strength and also is responsible for maintaining thephysical location of the chondrocyte. Proteoglycans andnoncollagenous proteins bind to the collagenous mesh-work or become mechanically entrapped within it, andwater fills this molecular framework. Some noncollage-nous proteins help organize and stabilize the matrix mac-romolecular framework whereas others help chondrocytesbind to the macromolecules of the matrix.
Articular cartilage, like most tissues, contains multiplegenetically distinct collagen types, the major ones beingcollagen types II, VI, IX, X and XI. Collagen types II, IXand XI form the cross-banded fibrils seen by electron mi-croscopy (Figure 3). The organization of these fibrils into atight meshwork that extends throughout the tissue pro-
Figure 3 Electro n micro gra p hs sh o w in g t h e su p erficial z o n e (A), tra nsit io n al z o n e (B), u p p er p ortio n o f t h e mid dle (ra dial or d e e p)z o n e (C), a n d lo w er p ortio n o f t h e mid dle z o n e (D) o f t h e articular cartila g e in t ert errit orial m a trix fro m t h e m e dial f e m oral co n dyleo f a n 8-m o n t h-old ra b bit . A rro ws in dica t e pro t e o glyca ns precipit a t e d w it h ru t h e niu m h exa min e trichlorid e . Bar = 0.5 n m . (Re pro-d uce d fro m Buck w alt er JA , H u n zik er EB, Rose n b erg LC, e t al: A rticular cartila g e: Co m p osit io n a n d struct ure , in W o o SL, Buck w alt erJA (e ds): Injury a n d Re p air o f t h e M usculosk ele t al So f t Tissu es. Park Rid g e , IL, A m erica n Aca d e my o f O rt h o p a e dic Surg e o ns, 1988, p p405-425.)
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163American Academy of Orthopaedic Surgeons | Orthopaedic Basic Science, ed 3
Zona media o radial • Condrocitos de forma esferoidal alineados en columnas perpendiculares a la superficie
• Fibras de colágeno de mayor diámetro • Mayor concentración de proteoglicanos • Menor concentración de agua • Resiste la fuerza de cizallamiento
tial for cartilage resiliency and joint lubrication or in theconcentrations of collagen and proteoglycans. It is clear,however, that the chondrocytes are in large measure re-sponsible for the maintenance and structural competence
of these materials and for allowing them to carry out theirrequired activities and functions. The chondrocytes areresponsible for producing and replacing appropriateamounts of macromolecules and assembling them into ahighly ordered macromolecular framework. To accom-plish these activities, the cells must sense changes in thematrix composition caused by degradation of macromol-ecules and the mechanical demands placed on the articu-lar surface, and then respond by synthesizing appropriatetypes and amounts of macromolecules.
Aging profoundly alters chondrocyte function. Withaging, the capacity of the cells to synthesize some types ofproteoglycans, their proliferative capacity, and their re-sponse to anabolic stimuli (including growth factors) de-creases. These changes may limit the ability of the cells tomaintain and restore the tissue and thereby contribute tothe development and progression of articular cartilage de-generation.
Extracellular M a trixThe articular cartilage matrix consists of two compo-nents: the tissue fluid and the framework of structuralmacromolecules that give the tissue its form and stability.The interaction of the tissue fluid and the macromolecu-lar framework give the tissue its mechanical properties ofstiffness and resilience. Water contributes up to 80% of
Figure 1 A rticular cartila g e fro m t h e m e dial f e m oral co n dyleo f a n 8-m o n t h-old ra b bit . Th e tissu e is org a niz e d in t o f o ur lay-ers or z o n es: t h e su p erficial z o n e (S), t h e tra nsit io n al z o n e (T),t h e mid dle (ra dial or d e e p) z o n e (M), a n d t h e calcif ie d cartila g ez o n e (C). Bar = 50 n m . (Re pro d uce d fro m Buck w alt er JA , H u n-zik er EB, Rose n b erg LC, e t al: A rticular cartila g e: Co m p osit io na n d struct ure , in W o o SL, Buck w alt er JA (e ds): Injury a n d Re p airo f t h e M usculosk ele t al So f t Tissu es. Park Rid g e , IL, A m erica nAca d e my o f O rt h o p a e dic Surg e o ns, 1988, p p 405-425.)
Figure 2 Electro n micro gra p hs sh o w in g t h e su p erficial z o n e (A), tra nsit io n al z o n e (B), mid dle (ra dial or d e e p) z o n e (C), a n d calci-f ie d cartila g e z o n e (D) o f m a t ure articular cartila g e ch o n drocyt es fro m t h e m e dial f e m oral co n dyle o f a ra b bit . N = n ucle us, G =glyco g e n , IF = in t erm e dia t e fila m e n ts, M M = min eraliz e d m a trix, U M = u n min eraliz e d m a trix, b ar = 3 n m . (Re pro d uce d fro m Buck-w alt er JA , H u n zik er EB, Rose n b erg LC, e t al: A rticular cartila g e: Co m p osit io n a n d struct ure , in W o o SL, Buck w alt er JA (e ds): Injury a n dRe p air o f t h e M usculosk ele t al So f t Tissu es. Park Rid g e , IL, A m erica n Aca d e my o f O rt h o p a e dic Surg e o ns, 1988, p p 405-425.)
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the weight of articular cartilage and the interaction of wa-ter with the matrix macromolecules significantly influ-ences the mechanical properties of the tissue. Some of thewater is in the form of a gel and thus with pressure canmove freely in and out of the tissue. With pressure on thecartilage the water may move out of the tissue and form arelationship with the cartilage surface, which then servesas the lubrication system for cartilage movement on carti-lage. The volume, concentration, and behavior within thetissue depends primarily on its interaction with the struc-tural macromolecules: in particular, the large aggregatingproteoglycans that help maintain the fluid within the ma-trix and the fluid electrolyte concentrations. Because thesemacromolecules have large numbers of negative chargesthat attract positively charged ions and repel negativelycharged ions, they increase the concentration of positiveions such as sodium and decrease the concentration ofnegative ions such as chloride. The increase in total inor-ganic ion concentration increases the tissue osmolarity.
Struct ural M acro m oleculesThe cartilage structural macromolecules, collagens, pro-teoglycans, and noncollagenous proteins contribute 20%to 40% of the wet weight of the tissue. The three classes of
macromolecules differ in their concentrations within thetissue and in their contributions to the tissue properties.Collagens contribute about 60% of the dry weight ofcartilage, proteoglycans contribute 25% to 35%, and thenoncollagenous proteins and glycoproteins contribute15% to 20%. Collagens are distributed relatively uni-formly throughout the depth of the cartilage, except forthe collagen-rich superficial zone (“the skin” of cartilagein which the collagen fibers run parallel the surface). Thecollagen fibrillar meshwork gives cartilage its form andtensile strength and also is responsible for maintaining thephysical location of the chondrocyte. Proteoglycans andnoncollagenous proteins bind to the collagenous mesh-work or become mechanically entrapped within it, andwater fills this molecular framework. Some noncollage-nous proteins help organize and stabilize the matrix mac-romolecular framework whereas others help chondrocytesbind to the macromolecules of the matrix.
Articular cartilage, like most tissues, contains multiplegenetically distinct collagen types, the major ones beingcollagen types II, VI, IX, X and XI. Collagen types II, IXand XI form the cross-banded fibrils seen by electron mi-croscopy (Figure 3). The organization of these fibrils into atight meshwork that extends throughout the tissue pro-
Figure 3 Electro n micro gra p hs sh o w in g t h e su p erficial z o n e (A), tra nsit io n al z o n e (B), u p p er p ortio n o f t h e mid dle (ra dial or d e e p)z o n e (C), a n d lo w er p ortio n o f t h e mid dle z o n e (D) o f t h e articular cartila g e in t ert errit orial m a trix fro m t h e m e dial f e m oral co n dyleo f a n 8-m o n t h-old ra b bit . A rro ws in dica t e pro t e o glyca ns precipit a t e d w it h ru t h e niu m h exa min e trichlorid e . Bar = 0.5 n m . (Re pro-d uce d fro m Buck w alt er JA , H u n zik er EB, Rose n b erg LC, e t al: A rticular cartila g e: Co m p osit io n a n d struct ure , in W o o SL, Buck w alt erJA (e ds): Injury a n d Re p air o f t h e M usculosk ele t al So f t Tissu es. Park Rid g e , IL, A m erica n Aca d e my o f O rt h o p a e dic Surg e o ns, 1988, p p405-425.)
Chapter 9 Articular Cartilage and Osteoarthritis
163American Academy of Orthopaedic Surgeons | Orthopaedic Basic Science, ed 3
Zona de car$lago calcificado • Separa la zona radial del hueso subcondral • Las células con$enen un reDculo endoplasmico y aparato de Golgi pequeño.
• Nivel metabólico muy bajo, no funcionales
tial for cartilage resiliency and joint lubrication or in theconcentrations of collagen and proteoglycans. It is clear,however, that the chondrocytes are in large measure re-sponsible for the maintenance and structural competence
of these materials and for allowing them to carry out theirrequired activities and functions. The chondrocytes areresponsible for producing and replacing appropriateamounts of macromolecules and assembling them into ahighly ordered macromolecular framework. To accom-plish these activities, the cells must sense changes in thematrix composition caused by degradation of macromol-ecules and the mechanical demands placed on the articu-lar surface, and then respond by synthesizing appropriatetypes and amounts of macromolecules.
Aging profoundly alters chondrocyte function. Withaging, the capacity of the cells to synthesize some types ofproteoglycans, their proliferative capacity, and their re-sponse to anabolic stimuli (including growth factors) de-creases. These changes may limit the ability of the cells tomaintain and restore the tissue and thereby contribute tothe development and progression of articular cartilage de-generation.
Extracellular M a trixThe articular cartilage matrix consists of two compo-nents: the tissue fluid and the framework of structuralmacromolecules that give the tissue its form and stability.The interaction of the tissue fluid and the macromolecu-lar framework give the tissue its mechanical properties ofstiffness and resilience. Water contributes up to 80% of
Figure 1 A rticular cartila g e fro m t h e m e dial f e m oral co n dyleo f a n 8-m o n t h-old ra b bit . Th e tissu e is org a niz e d in t o f o ur lay-ers or z o n es: t h e su p erficial z o n e (S), t h e tra nsit io n al z o n e (T),t h e mid dle (ra dial or d e e p) z o n e (M), a n d t h e calcif ie d cartila g ez o n e (C). Bar = 50 n m . (Re pro d uce d fro m Buck w alt er JA , H u n-zik er EB, Rose n b erg LC, e t al: A rticular cartila g e: Co m p osit io na n d struct ure , in W o o SL, Buck w alt er JA (e ds): Injury a n d Re p airo f t h e M usculosk ele t al So f t Tissu es. Park Rid g e , IL, A m erica nAca d e my o f O rt h o p a e dic Surg e o ns, 1988, p p 405-425.)
Figure 2 Electro n micro gra p hs sh o w in g t h e su p erficial z o n e (A), tra nsit io n al z o n e (B), mid dle (ra dial or d e e p) z o n e (C), a n d calci-f ie d cartila g e z o n e (D) o f m a t ure articular cartila g e ch o n drocyt es fro m t h e m e dial f e m oral co n dyle o f a ra b bit . N = n ucle us, G =glyco g e n , IF = in t erm e dia t e fila m e n ts, M M = min eraliz e d m a trix, U M = u n min eraliz e d m a trix, b ar = 3 n m . (Re pro d uce d fro m Buck-w alt er JA , H u n zik er EB, Rose n b erg LC, e t al: A rticular cartila g e: Co m p osit io n a n d struct ure , in W o o SL, Buck w alt er JA (e ds): Injury a n dRe p air o f t h e M usculosk ele t al So f t Tissu es. Park Rid g e , IL, A m erica n Aca d e my o f O rt h o p a e dic Surg e o ns, 1988, p p 405-425.)
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Interacción Matriz -‐Condrocito • En respuesta a diferentes esDmulos • Autocrino o paracrino
– Interleucina 1 • Metaloproteasas
– Degradan macromoléculas – Interfieren en la síntesis te proteoglicanos
– Factor de crecimiento dependiente de insulina 1 – Factor de crecimiento transformador beta
• Es$mulan la síntesis de matriz extracelular y proliferación celular
Biomecánica • Cargas mecánicas está$cas y dinámicas
– Compresión (red fibrilar) Colágeno • .5 a 1 MPa
– Cizallamiento (red fibrilar) Colágeno • .25 MPa
– Tensión (Proteoglicanos) • 10 a 50 MPa
La habilidad del carDlago para resis$r las fuerzas de compresión, tensión y cizallamiento depende de la composición e integridad de l matriz extracelular
ents, substrates for synthesis of matrix molecules, newlysynthesized molecules, degraded matrix molecules, meta-bolic waste products and molecules that help regulate cellfunction, such as cytokines and growth factors, all passthrough the matrix, and in some instances may be storedin the matrix.
Throughout life, chondrocytes degrade and synthesizematrix macromolecules. The mechanisms that control thebalance between these activities remain poorly under-stood, but cytokines with catabolic and anabolic effectsappear to have important roles. For example, interleukin 1(IL-1) induces expression of matrix metalloproteases thatcan degrade the matrix macromolecules and interfereswith synthesis of matrix proteoglycans at the transcrip-tional level. Other cytokines such as insulin-dependentgrowth factor I and transforming growth factor beta op-pose these catabolic activities by stimulating matrix syn-
thesis and cell proliferation. In response to a variety ofstimuli, chondrocytes synthesize and release these cytok-ines into the matrix where they may bind to receptors onthe cell surfaces (stimulating cell activity either by auto-crine or paracrine mechanisms) or become trappedwithin the matrix. The degradative response, on the otherhand, appears to be the result of a complex cascade thatincludes IL-1, stromelysin, aggrecanase, plasmin, and col-lagenase being activated or inhibited by factors such asprostaglandins, transforming growth factors beta, tumornecrosis factor, tissue inhibitors of metalloproteases, tissueplasminogen activator, plasminogen activator inhibitor,and other molecules.
Articular Cartilage BiomechanicsArticular cartilage is subjected to a wide range of staticand dynamic mechanical loads. Under normal physiologic
Figure 7 Lo a din g o f articular cartila g e ca uses tissu e d e f orm a tio n a n d ch a n g es in t h e cellular micro e nviro n m e n t . D urin g join t m o-tio n (A), articular cartila g e (gray) is su bject e d t o a co m plex co m bin a tio n o f co m pressio n a n d sh e ar f orces, ca usin g d e f orm a tio n o f t h ecells a n d extracellular m a trix as w ell as f luid a n d io n flo ws. M e t h o d olo gies d evelo p e d t o m e asure cartila g e bio m ech a nical pro p ertiesu n d er hydrost a tic (or osm o tic) pressure lo a din g (B), u nco n fin e d (C) a n d co n fin e d (D) co m pressio n , sh e ar (E), a n d t e nsio n h ave b e e nuse d t o q u a n tify t h e m e t a b olic resp o nse o f articular cartila g e t o n orm al a n d injurio us m ech a nical lo a ds. (A d a p t e d w it h p ermissio nfro m D e M icco M , Kim YJ, Gro d zinsky AJ: Resp o nse o f t h e ch o n drocyt e t o m ech a nical stim uli, in Bra n d t K , D o h erty M , Lo h m a n d er S(e ds): Ost e o art hritis. O xf ord , En gla n d , O xf ord U niversity Press, 2003.)
Chapter 9 Articular Cartilage and Osteoarthritis
167American Academy of Orthopaedic Surgeons | Orthopaedic Basic Science, ed 3
Cuando el cartilago es comprimido expulsa agua/solutos de proteoglicanos , éstos balanceando las cargas
Osteoartrosis
Perdida progresiva de la estructura y función normal del carDlago ar$cular, acompañado por
un intento de reparación del mismo
Osteoartri$s
• Se desarrolla frecuentemente en ausencia de una causa aparente (primaria o idiopá$ca)
• Secundarias – Daño ar$cular – Infección – Desordenes neurológicos, metabólicos, hereditarios
Osteoartri$s
• Primaria o Idiopá$ca – Edad, predisposición gené$ca, desordenes metabólicos y hormonales, inflamación
– Peso – Ac$vidad fisica – Incidencia y prevalencia aumenta >40 años
Osteoartri$s
• Secundaria – La edad de inicio depende de la causa – Deformidades (displasia del desarrollo de la cadera)
– Se puede presentar en adultos jóvenes e incluso en niños
Osteoartrosis • Rodillas
• Caderas
• Pie
• Columna
• Manos
Osteoartri$s • Síntomas y signos
– Dolor
– Limitación de la movilidad
– Crepitación
– Inflamación
– Deformidad
Osteoartrosis
• Tejidos involucrados – Tejido sinovial – Car$lago ar$cular – Hueso subcondral y metafisiario – Ligamentos – Capsula ar$cular – Músculos
Cambio Primario Perdida del car$lago ar$cular, remodelación de hueso
subcondral y formación de osteofitos.
Osteoartrosis • Microscópicos + tempranos
– Deshilachamiento o desfibrilación de la zona superficial hasta transicional del carDlago ar$cular.
– Disminución del la $nción de proteoglicanos en zonas superficial y transicional
– Cambio la vascularidad subcondral.
Osteoartrosis • Visibles + tempranos
– Desfibrilación o disrupción de las capas superficiales del carDlago ar$cular
• Progresión – Hendiduras, la superficie ar$cular se vuelve rugosa e irregular
– Las hendiduras y fibrilación alcanzan el hueso subcondral
– Se liberan fragmentos libres ar$culares y disminuye el grosor del carDlago.
– Al mismo $empo existe una degeneración enzimá$ca de la matriz
Osteoartrosis
Osteoartrosis
• Los mecanismos responsables de la progresión no están claros
• Proceso en 3 fases 1.-‐Alteración o daño en la matriz del car$lago 2.-‐ Respuesta de los condrocitos al daño del tejido 3.-‐ Disminución de la respuesta sinté$ca de los condrocitos y progresión de la perdida de tejidos
Osteoartri$s • 1º Fase. Causas
– Carga torsional o impacto de alta intensidad
– Inflamación Ar$cular
– Cambios metabólicos en el tejido
Osteoartri$s • 1º Fase
– Disrupción de la estructura macromolecular en incremento en el contenido de agua.
– Colágeno $po II permanece constante – Disminuye agregación de proteoglicanos – Agrecanos
• Disminución de la longitud y de las cadenas de glucosaminoglicanos.
Disminución en la rigidez de la matriz extracelular
Osteoartrosis • 2º Fase
Condrocitos detectan daño en los tejidos o alteración en la osmolaridad, densidad o estructura y liberan mediadores que es$mulan la respuesta celular
Osteoartri$s • 2º Fase. Respuesta
– Ac$vidad anabólica y catabólica – Respuesta Anabólica
• Proliferación de condroci$ca • Síntesis de matriz extracelular
– Respuesta Catabólica • Producción de Oxido Nítrico • Producción de Interleucina 1
Condrocitos Liberación en respuesta a
un estrés
Oxido nítrico
Interleucina 1
Metaloproteasas
Degradación de las moléculas de la matriz
(fibronec@na)
Interleucina 1
Osteoartri$s • 3º Fase
– Falla en estabilizar o restaurar el tejido. • Daño progresivo el carDlago ar$cular • Disminución en la respuesta anabólica de los condrocitos • Osteoartrosis
Osteoartri$s • Alteraciones del hueso subcondral
– Incremento en la densidad del hueso subcondral o esclerosis subcondral
• (Primer signo de enf. ar$cular degenera$va en hueso subcondral)
– Formación de cavidades óseas en forma de quiste con tejido mixoide, fibroso o car$laginoso
– Apariencia de car$lago regenera$vo en o sobre el hueso subcondral. OSTEOFITOS
Osteoartri$s
• Acortamiento
• Deformidad
• Inestabilidad
Tratamiento
• Objetivos – Alivio de sintomas – Mantener/mejorar función – Limitar incapacidad física – Evitar toxicidad medicamentosa