科研之友
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摘要
Bone morphogenetic proteins (BMP) stimulate osteoblast differentiation by signal transduction via three BMP receptors (BMPR-1A, 1B, and -11A). Several growth factors, including transforming growth factor-beta (TGF-beta 1), fibroblast growth factor-2 (FGF-2) and platelet-derived growth factor-AB (PDGF-AB), have also been shown to play an important part in osteogenesis. The mechanism underlying these activities is unclear, but these growth factors could modulate the BMP/BMPR pathway by up-regulating BMPR expression, thereby enhancing the osteogenic responses of bone cells to the BMP. In this study we have therefore examined the effects of TGF-beta 1, FGF-2, and PDGF-AB on BMPR expression and BMP-2-mediated osteoblast functions in primary human bone cells. The results showed that although the ligand BMP-2 and growth factors had little effect on BMPR-1A and -11 transcript expression, they significantly up-regulated BMPR-1B mRNA specifically. However, only the growth factors, but not the ligand BMP2, increased the surface expression of the BMPR-1B antigen, which was found to be due to a differential effect of BMP-2 and the growth factors on the Smurf1/Smad6-induced breakdown process. Pre-incubation of the cells with the growth factors significantly augmented BMP-2-induced Smad1/5/8 phosphorylation, and Dlx5 expression ALP activity, compared with that of cell streated with BMP-2 alone. When cells were transfected with siRNA targeting BMPR-1B, the growth factors neither up-regulated BMPR-1B transcript expression nor enhanced BMP-2-induced Smad1/5/8 phosphorylation, Dlx5 expression and ALP activity. The results indicate that increased BMPR-1B by TGF-beta 1, FGF-2, and PDGF-AB significantly enhances BMP-2-induced osteogenic functions in vitro, suggesting that they might positively modulate bone formation by up-regulating BMPR-1B in vivo.
- 出版日期2006-12
