Dr. Laura Amundson - Initiation of Bone Lesions in Young Growing Pigs and the Importance of Maternal Nutrition
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Initiation of Bone Lesions in Young Growing Pigs and the Importance of Maternal Nutrition - Dr. Laura Amundson, Post-Doctoral Fellow, Lactation Biology, University of Wisconsin-Madison, Dairy Science, from the 2016 Allen D. Leman Swine Conference, September 17-20, 2016, St. Paul, Minnesota, USA. More presentations at http://www.swinecast.com/2016-leman-swine-conference-material
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Dr. Laura Amundson - Initiation of Bone Lesions in Young Growing Pigs and the Importance of Maternal Nutrition
- 1. Initiation of bone lesions in young growing pigs and the importance of maternal nutrition Allen D. Leman Swine Conference Laura Amundson University of Wisconsin-Madison September 19, 2016
- 2. 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
- 3. Kyphosis – idiopathic disease induced by vitamin D, Ca & P deficiencies Rortvedt et al., 2012.Hypovitaminosis D kyphotic pig model
- 4. Femur Hypovitaminosis D Induced Kyphosis Abnormalities detected in multiple locations Vertebrae -D +D
- 5. Histology Part #1 The anterior vertebral endplates of the kyphotic vertebrae (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?
- 6. z Growth plate Resting zone Proliferative zone Hypertrophic zone Invading capillary Osteoblast Osteoclast Endochondral Ossification
- 7. Amundson et al., 2016 (not yet reported) Hypovitaminosis D Induced Kyphosis Maternal Diet Carryover Effect
- 8. Which signaling pathways are altered by hypovitaminosis D to induce gross bone lesions and abnormalities?
- 9. Factors Important in Bone Matrix Turnover • Matrix Metalloproteinases (MMP) • MMP9 (gelatinase) • MMP13 (collagenase) • Zinc dependent enzymes • Vascular Endothelial Growth Factor (VEGF)
- 10. z Growth plate Type II Collagen Type X Collagen MMP13 VEGF MMP9 MMP13 VEGF Type I Collagen
- 11. VEGF ECM VEGF MMP13 MMP9 MMP13 MMP9 VEGF chondrocyte osteoblast osteoclast Adapted from Lin et al., 2002
- 12. VEGF ECM VEGF MMP13 MMP9 MMP13 MMP9 VEGF VEGF chondrocyte osteoblast osteoclast Angiogenesis Adapted from Lin et al., 2002
- 13. VEGF ECM VEGF MMP13 MMP9 MMP13 MMP9 VEGF chondrocyte osteoblast osteoclast VEGF Angiogenesis Adapted from Lin et al., 2002
- 14. Molecular Data • Initial hypothesis: • Decreased expression of femur and vertebrae MMP9, MMP13, and VEGF mRNA
- 15. Femur Relative MMP9 mRNA expression Femur relative MMP9
- 16. 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
- 18. 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!
- 19. Swine Research & Teaching Center SRTC Staff Jamie Reichert Jeff Booth Sam Trace Keri Graff Lab Support Laura Hernandez Jimena Laporta Acknowledgements Tom Crenshaw
- 20. Questions