1 alpha,25-dihydroxyvitamin D3 increases TGF beta 1 binding to human osteoblasts

Abstract

1alpha,25-Dihydroxyvitamin D3 (1alpha,25(OH)2D3) increases the binding of transforming growth factor beta1(TGF beta1) via TGF beta receptors to the surface of human osteoblasts. The increase in TGF beta receptors induced by 1alpha,25(OH)2D3 is dependent on increases in TGF beta secretion induced by 1alpha,25(OH)2D3, since antibodies directed against TGF beta block the increase in TGF beta1 binding. The increase in TGF beta type I and II receptors on cell surfaces following 1alpha,25(OH)2D3 treatment is associated with increases in receptor mRNA concentrations. Increases in receptor mRNA concentrations following 1alpha,25(OH)2D3 treatment are not due to changes in receptor gene transcription. The role of TGF beta receptors, in mediating the growth responses to 1alpha,25(OH)2D3 is demonstrated by showing that osteoblasts which express dominant negative, kinase-deficient TGF beta type II receptors, fail to respond to the growth-inhibitory effects of 1alpha,25(OH)2D3. An increase in TGF beta receptor expression is important in mediating 1alpha,25(OH)2D3-associated changes in the growth rate of osteoblasts.