Date of Award

2009

Degree Type

Thesis

Degree Name

Master of Science

Program

Physiology

Supervisor

Dr. Kaiping Yang

Abstract

This study was designed to test the hypothesis that bone morphogenetic protein-3 (BMP-3) promotes adipogenesis using C3H10T1/2 mesenchymal stem cells (MSCs) and 3T3-L1 preadipocytes as in vitro model systems. Although having no effects on the commitment of C3H10T1/2 cells to the adipocyte lineage or the differentiation of 3T3-L1 preadipocytes to adipocytes, BMP-3 stimulated DNA synthesis (as determined by [3H]- thymidine incorporation) in both cell types. Furthermore, the mitogenic effects of BMP-3 were mediated by the TGF-p/activin signalling pathway, because BMP-3 activated the TGF-p/activin pathway in C3H10T1/2 cells, and the TGF-p/activin pathway inhibitor SB- 431542 blocked BMP-3-stimulated proliferation. Additionally, inhibitors of ERK1/2 and p38 MAPK pathways reduced proliferation under basal conditions. In conclusion, the present study demonstrates that BMP-3 stimulates proliferation of MSCs and preadipocytes in vitro, which provides a source for adipogenesis. Consequently, aberrant BMP-3 expression may have consequences not only for normal adipose tissue growth but also for the pathogenesis of obesity.

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