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1 alpha,25-Dihydroxyvitamin D3 increases transforming growth factor and transforming growth factor receptor type I
Y Wu1, J D Haugen, A R Zinsmeister
1Nephrology Research Unit, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Abstract:
To determine whether the inhibition of human osteoblast growth mediated by 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)D3) occurs as a result of changes in transforming growth factor (TGF) and TGF receptor synthesis, we examined the effects of 1 alpha,25(OH)2D3 on the synthesis of TGF beta and TGF-beta receptors. Treatment with 1 alpha,25(OH)2D3, but not vehicle, increased TGF-beta 2 concentrations in human osteoblast cell supernantants in a dose- and time-dependent manner. The increase in TGF-beta 2 concentrations was associated with an inhibition of osteoblast cell growth; antibodies directed against transforming growth factor beta partially blocked the inhibition of cellular growth mediated by 1 alpha,25-(OH)2D3 TGF-beta 2 gene transcription and TGF-beta 2 mRNA concentrations were increased in 1 alpha,25(OH)D3 but not in vehicle-treated cells. 1 alpha,25(OH)2D3 increased TGF-beta type I and type II receptor mRNA levels in osteoblasts. Increased expression of TGF-beta 2 and TGF-beta receptors by 1 alpha,25(OH)2D3 might account for the inhibition of human osteoblast growth seen following 1 alpha,25(OH)2D3 treatment.