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

Biochem Biophys Res Commun. 1997 Oct 29;239(3):734-9. doi: 10.1006/bbrc.1997.7544.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Activin Receptors, Type I*
  • Antibodies / pharmacology
  • Calcitriol / antagonists & inhibitors
  • Calcitriol / immunology
  • Calcitriol / pharmacology*
  • Cell Line
  • Cell-Free System
  • Dose-Response Relationship, Drug
  • Fetus
  • Growth Inhibitors / antagonists & inhibitors
  • Growth Inhibitors / immunology
  • Growth Inhibitors / pharmacology
  • Growth Substances / metabolism
  • Humans
  • Osteoblasts / cytology
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism*
  • Protein-Serine-Threonine Kinases / biosynthesis*
  • Protein-Serine-Threonine Kinases / genetics
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / biosynthesis*
  • Receptors, Transforming Growth Factor beta / genetics
  • Transcription, Genetic / drug effects
  • Transforming Growth Factor beta / biosynthesis*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / immunology

Substances

  • Antibodies
  • Growth Inhibitors
  • Growth Substances
  • RNA, Messenger
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta
  • Protein-Serine-Threonine Kinases
  • Activin Receptors, Type I
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptor, Transforming Growth Factor-beta Type II
  • Calcitriol