Dr. Laura Amundson - Initiation of Bone Lesions in Young Growing Pigs and the Importance of Maternal...
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Transcript of Dr. Laura Amundson - Initiation of Bone Lesions in Young Growing Pigs and the Importance of Maternal...
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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
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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
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Kyphosis – idiopathic disease induced by vitamin D, Ca & P deficiencies
Rortvedt et al., 2012.Hypovitaminosis D kyphotic pig model
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Femur
Hypovitaminosis D Induced KyphosisAbnormalities detected in multiple locations
Vertebrae
-D
+D
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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?
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z
Growth plate
Resting zone
Proliferative zone
Hypertrophic zone
Invading capillary
Osteoblast
Osteoclast
Endochondral Ossification
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Amundson et al., 2016 (not yet reported)
Hypovitaminosis D Induced KyphosisMaternal Diet Carryover Effect
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Which signaling pathways are altered by hypovitaminosis D to induce gross bone lesions
and abnormalities?
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Factors Important in Bone Matrix Turnover
• Matrix Metalloproteinases (MMP)• MMP9 (gelatinase)• MMP13 (collagenase)• Zinc dependent enzymes
• Vascular Endothelial Growth Factor (VEGF)
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z
Growth plate
Type II Collagen
Type X CollagenMMP13VEGF
MMP9
MMP13VEGF
Type I Collagen
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VEGF
ECM
VEGF
MMP13
MMP9
MMP13MMP9
VEGF
chondrocyte
osteoblast
osteoclast
Adapted from Lin et al., 2002
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VEGF
ECM
VEGF
MMP13
MMP9
MMP13MMP9
VEGF VEGF
chondrocyte
osteoblast
osteoclast
Angiogenesis
Adapted from Lin et al., 2002
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VEGF
ECM
VEGF
MMP13
MMP9
MMP13MMP9VEGF
chondrocyte
osteoblast
osteoclast
VEGF
Angiogenesis
Adapted from Lin et al., 2002
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Molecular Data
• Initial hypothesis:• Decreased expression of femur and vertebrae
MMP9, MMP13, and VEGF mRNA
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Femur Relative MMP9 mRNA expression
Femur relative MMP9
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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
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Interactions and Balance
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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!
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Swine Research & Teaching Center
SRTC Staff
Jamie ReichertJeff BoothSam TraceKeri Graff
Lab Support
Laura HernandezJimena Laporta
AcknowledgementsTom Crenshaw
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Questions