BMP-1 inhibitor and TNF-a effects on bone matrix deposition
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Abstract
Bone matrix synthesis and deposition play an important role in bone physiology. Any disturbance can lead to several pathologies. We know that osteoblasts produce a large amount of collagen and that those molecules are subsequently crosslinked by lysyl oxidase. Lysyl oxidase is processed to its mature fom by procollagen C-proteinase (BMP-1). TNF-[alpha] is an inflammatory cytokine that has multiple effects on osteoblasts. Our goal was to study the effects of first, a hydroxamic acid procollagen C proteinase inhibitor provided by FibroGen Corporation, and second, the effects of TNF-[alpha] on collagen deposition and cross-linking by osteoblasts. In the first part of our study, MC3T3-E1 osteoblast like cells were grown in differentiation medium for 15 and 20 days in the presence or absence of the procollagen C-proteinase (BMP-1) inhibitor and the amount of mature crosslinks (Pyd/Dpd) was assessed by enzyme immuno assay. In the second part of our study, MC3T3-E1 cells were grown in differentiation medium in the presence or absence of TNF-[alpha] for 24 hours and subsequently pulsed labeled with tritiated proline for 2 hours. A collagen synthesis assay was performed to evaluate the amount of collagen peptides produced. Our data shows that the procollagen C-proteinase inhibitor at 20 and 50 [mu]M may increase abnormal collagen deposition but doesn’t seem to modify much the mature collagen cross-1inking process. TNF-[alpha] has little or no effect on collagen synthesis. Other lysyl oxidase iso enzymes, not affected by our BMP-1 inhibitor, may be invoIved in mature crosslink production. TNF-[alpha]’s effects on collagen are mainly extracellular and include inhibition of lysyl oxidase production.
Description
Thesis (MSD)--Boston University, Goldman School of Dental Medicine, 2006 (Periodontology and Oral Biology).
Includes bibliographical references: leaves 72-86.
Includes bibliographical references: leaves 72-86.
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