Glucocorticoids decrease vitamin D receptor number and gene expression in human osteosarcoma cells

J Bone Miner Res. 1992 Jan;7(1):21-7. doi: 10.1002/jbmr.5650070105.


The mechanisms by which glucocorticoids (GC) inhibit some actions of vitamin D [1,25-(OH)2D3] are not well understood, but there is growing evidence that GC alter vitamin D receptor (VDR) number. We studied the effects of dexamethasone (DEX) on VDR number and mRNA in the human osteosarcoma cell line, MG-63. The effects of DEX on 1,25-(OH)2D3 binding were examined by incubating confluent cells overnight in media without or with 10(-6) M DEX. DEX decreased VDR number (B max) by approximately 70% (110 versus 32 fmol/mg cellular protein, p less than 0.001) without significantly changing the apparent affinity (K'D) of 1,25-(OH)2D3 for its receptor (3.8 versus 2.2 x 10(-10) M, p greater than 0.05). Overnight incubation of MG-63 cells with DEX produced a time- and dose-responsive decrease in VDR mRNA compared to untreated controls (p less than 0.01). To determine the mechanism of the DEX-mediated decrease in VDR mRNA, the effect of DEX on VDR mRNA stability was studied. We found that the half-life for the VDR mRNA was approximately 5.7 h and was not significantly changed when the cells were incubated with DEX (approximately 6.3 h). We conclude that DEX decreases both VDR number and mRNA in MG-63 osteosarcoma cells. Since the half-life of VDR mRNA was not significantly modified by dexamethasone, glucocorticoids appear to decrease VDR mRNA by inhibiting VDR gene transcription or by affecting the processing of VDR mRNA.

Publication types

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

MeSH terms

  • Actins / drug effects
  • Actins / genetics
  • Blotting, Northern
  • Calcitriol / metabolism
  • Dexamethasone / pharmacology*
  • Gene Expression Regulation / drug effects*
  • Histones / drug effects
  • Histones / genetics
  • Humans
  • Kinetics
  • Osteoblasts / drug effects*
  • Osteoblasts / metabolism
  • RNA, Messenger / drug effects
  • Receptors, Calcitriol
  • Receptors, Steroid / drug effects*
  • Receptors, Steroid / genetics
  • Receptors, Steroid / metabolism
  • Tumor Cells, Cultured


  • Actins
  • Histones
  • RNA, Messenger
  • Receptors, Calcitriol
  • Receptors, Steroid
  • Dexamethasone
  • Calcitriol