1α,25-dihydroxyvitamin D₃ increases transforming growth factor and transforming growth factor receptor type I and II synthesis in human bone cells

To determine whether the inhibition of human osteoblast growth mediated by 1α,25-dihydroxyvitamin D₃ (1α,25(OH)D₃) occurs as a result of changes in transforming growth factor (TGF) and TGF receptor synthesis, we examined the effects of 1α,25(OH)₂D₃ on the synthesis of TGFβ and TGF-β receptors. Treatment with 1α,25(OH)₂D₃, but not vehicle, increased TGF-β2 concentrations in human osteoblast cell supernantants in a dose- and time-dependent manner. The increase in TGF-β2 concentrations was associated with an inhibition of osteoblast cell growth; antibodies directed against transforming growth factor β partially blocked the inhibition of cellular growth mediated by 1α,25(OH)₂D₃. TGF-β2 gene transcription and TGF-β2 mRNA concentrations were increased in 1α,25(OH)D₃ but not in vehicle-treated cells. 1α,25(OH)₂D₃ increased TGF-β type I and type II receptor mRNA levels in osteoblasts. Increased expression of TGF-β2 and TGF-β receptors by 1α,25(OH)₂D₃ might account for the inhibition of human osteoblast growth seen following 1α,25(OH)₂D₃ treatment.