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-β (TGF-β) and 1(α,25-dihydroxyvitamin D₃ (1α,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-β stimulates osteoblast proliferation and growth, and inhibits the expression of the markers characteristic of the osteoblast phenotype such as osteocalcin. In contrast, 1(α,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-β and 1(α,25(OH)₂D₃ modulating their receptor expression, synthesis, and effects on osteoblast-specific gene expression. The cooperative actions of TGF-β and 1(α,25(OH)₂D₃ can be synergistic or antagonistic. It has recently been established that Smad proteins that transduce signals downstream the TGF-β stimulation may mediate the crosstalk between TGF-β and 1(α,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-β and 1(α,25(OH)₂D₃.