Regulation of osteoblast growth by interactions between transforming growth factor-beta and...

Osteoblast growth and differentiation encompass a series of events including proliferation, changes in cell shape, and expression of the markers specific for osteoblast phenotype. Both transforming growth factor-beta (TGF-beta) and 1alpha,25-dihydroxyvitamin D3 (1alpha,25[OH]2D3) are effective in regulating osteoblast proliferation, differentiation, bone matrix maturation and cell-specific gene expression. Although there is some degree of controversy regarding the influences on osteoblasts in vitro, it is generally agreed that TGF-beta stimulates osteoblast proliferation and growth, and inhibits the expression of the markers characteristic of the osteoblast phenotype such as osteocalcin. In contrast, 1alpha,25(OH)2D3 causes inhibition of the proliferation of osteoblasts, arrests their growth, and stimulates expression of specific markers. In many studies, complex interactions have been demonstrated between TGF-beta and 1alpha,25(OH)2D3 modulating their receptor expression, synthesis, and effects on osteoblast-specific gene expression. The cooperative actions of TGF-beta and 1alpha,25(OH)2D3 can be synergistic or antagonistic. It has recently been established that Smad proteins that transduce signals downstream the TGF-beta stimulation may mediate the crosstalk between TGF-beta and 1alpha,25(OH)2D3 signaling. Future studies should focus on the explanation of the molecular basis of these interactions and the in vivo consequences of the regulation of osteoblast growth and differentiation by TGF-beta and 1alpha,25(OH)2D3.