1-ALPHA,25-DIHYDROXYVITAMIN D-3 INCREASES TRANSFORMING-GROWTH-FACTOR AND TRANSFORMING-GROWTH-FACTOR RECEPTOR-TYPE-I AND RECEPTOR-TYPE-II SYNTHESIS IN HUMAN BONE-CELLS

To determine whether the inhibition of human osteoblast growth mediate d by 1 alpha,25-dihydroxyvitamin D-3 (1 alpha,25(OH)D-3) occurs as a r esult of changes in transforming growth factor (TGF) and TGF receptor synthesis, we examined the effects of 1 alpha,25(OH)(2)D-3 on the synt hesis of TGF beta and TGF-beta receptors. Treatment with 1 alpha,25(OH )(2)D-3, but not vehicle, increased TGF-beta 2 concentrations in human osteoblast cell supernantants in a dose-and time-dependent manner. Th e increase in TGF-beta 2 concentrations was associated with an inhibit ion of osteoblast cell growth; antibodies directed against: transformi ng growth factor beta partially blocked the inhibition of cellular gro wth mediated by 1 alpha,25(OH)D-3. TGF-beta 2 gene transcription and T DF-beta 2 mRNA concentrations were increased in 1 alpha,25(OH)D-3 but not in vehicle-treated cells. 1 alpha,25(OH)(2)D-3 increased TGF-beta type I and type II receptor mRNA levels in osteoblasts, Increased expr ession of TGF-beta 2 and TGF-beta receptors by 1 alpha,25(OH)(2)D-3 mi ght account for the inhibition of human osteoblast growth seen followi ng 1 alpha,25(OH)(2)D-3 treatment. (C) 1997 Academic Press.