1 alpha,25-dihydroxyvitamin D3 increases TGF beta 1 binding to human osteoblasts.
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.
Nagel
David
D
Nephrology Research Unit, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Kumar
Rajiv
R
D030201:Activin Receptors, Type I / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D005333:Fetus; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000096:biosynthesis; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D015854:Up-Regulation / Q000187:drug effects* / Q000235:genetics
D006131:Growth Inhibitors; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D002117:Calcitriol