dr. laura amundson - initiation of bone lesions in young growing pigs and the importance of maternal...
TRANSCRIPT
Initiation of bone lesions in young growing pigs and the importance of maternal
nutrition
Allen D. Leman Swine Conference
Laura AmundsonUniversity of Wisconsin-Madison
September 19, 2016
Outline
• Insights from the hypovitaminosis D kyphotic pig
• Endochondral ossification
• Molecular signals important in bone metabolism affected by vitamin D
• Conclusions on nutritional inputs to bone lesions
Kyphosis – idiopathic disease induced by vitamin D, Ca & P deficiencies
Rortvedt et al., 2012.Hypovitaminosis D kyphotic pig model
Femur
Hypovitaminosis D Induced KyphosisAbnormalities detected in multiple locations
Vertebrae
-D
+D
Histology Part #1
The anterior vertebral endplates of the kyphoticvertebrae (solid arrows) were less ossified than those of the control
vertebrae (dashed arrow), indicating that the deformity is likely a growth abnormality rather than an insufficiency type fracture.
Kyphotic
H&E
Trichrome
Control
H&E
Trichrome
Images courtesy of Dr. Matt Halanski
Uncoupled Endochondral Ossification?
z
Growth plate
Resting zone
Proliferative zone
Hypertrophic zone
Invading capillary
Osteoblast
Osteoclast
Endochondral Ossification
Amundson et al., 2016 (not yet reported)
Hypovitaminosis D Induced KyphosisMaternal Diet Carryover Effect
Which signaling pathways are altered by hypovitaminosis D to induce gross bone lesions
and abnormalities?
Factors Important in Bone Matrix Turnover
• Matrix Metalloproteinases (MMP)• MMP9 (gelatinase)• MMP13 (collagenase)• Zinc dependent enzymes
• Vascular Endothelial Growth Factor (VEGF)
z
Growth plate
Type II Collagen
Type X CollagenMMP13VEGF
MMP9
MMP13VEGF
Type I Collagen
VEGF
ECM
VEGF
MMP13
MMP9
MMP13MMP9
VEGF
chondrocyte
osteoblast
osteoclast
Adapted from Lin et al., 2002
VEGF
ECM
VEGF
MMP13
MMP9
MMP13MMP9
VEGF VEGF
chondrocyte
osteoblast
osteoclast
Angiogenesis
Adapted from Lin et al., 2002
VEGF
ECM
VEGF
MMP13
MMP9
MMP13MMP9VEGF
chondrocyte
osteoblast
osteoclast
VEGF
Angiogenesis
Adapted from Lin et al., 2002
Molecular Data
• Initial hypothesis:• Decreased expression of femur and vertebrae
MMP9, MMP13, and VEGF mRNA
Femur Relative MMP9 mRNA expression
Femur relative MMP9
Molecular Data
• Initial hypothesis:• Decreased expression of femur and vertebrae
MMP9, MMP13, and VEGF mRNA
• Articular joint diseases• Human, horse, and canine data• INCREASED MMPs• TIMPs – Tissue Inhibitor of Metalloproteinase
MMPs : TIMPs
Interactions and Balance
Conclusions• It’s complicated!
• Carryover of maternal nutrition is important in neonatal bone health
• Nutrients act locally (not just systemically) to couple endochondral ossification
• Nutrient interactions on molecular signaling in bone are not clearly established
• The kyphotic pig model provides a tool to understand the initiation and development of bone lesions
• Balance is key!
Swine Research & Teaching Center
SRTC Staff
Jamie ReichertJeff BoothSam TraceKeri Graff
Lab Support
Laura HernandezJimena Laporta
AcknowledgementsTom Crenshaw
Questions