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


, : Glucocorticoids decrease vitamin D receptor number and gene expression in human osteosarcoma cells. Journal of Bone and Mineral Research 7(1): 21-27

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.

US$19.90

PMID: 1312760

DOI: 10.1002/jbmr.5650070105


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