Regulation of osteoblast growth by interactions between transforming growth factor-β and 1α,25-dihydroxyvitamin D3

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 D-3 (1alpha,25[OH](2)D-3) 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)(2)D-3 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)(2)D-3 modulating their receptor expression, synthesis, and effects on osteoblast-specific gene expression. The cooperative actions of TGF-beta and 1alpha,25(OH)(2)D-3 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)(2)D-3 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)(2)D-3.