Hydrocortisone and Deflazacort Induce Different Effects on Vitamin D Receptor Level Increase Produced by 1,25-Dihydroxyvitamin D3 in Rat Osteoblast-like UMR-106 Cells

ROSA GUERRERO, CONCEPCIÓN de la PIEDRA, EMMA TEIXEIRO, RAFAEL BRAGADO, and MARIA LUISA TRABA

ABSTRACT.

Objective. The homologous upregulation produced by 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] on vitamin D receptor (VDR) levels, and the effects produced by the heterologous agents hydrocortisone or deflazacort, alone or in conjunction with this vitamin D metabolite, were studied in rat osteoblastic UMR-106 osteosarcoma cells.

Methods. VDR were determined by binding analysis (B_max and dissociation constant). VDR mRNA expression levels were measured by Northern blot analysis.

Results. Incubation with 10 nM 1,25(OH)₂D₃ produced a significant increase in B_max with respect to ethanol-treated cells (100.2 ± 13.2 vs 11.4 ± 4.8 fmol ³H-1,25(OH)₂D₃ bound/mg protein) together with a significant increase in VDR mRNA expression (483 ± 170% vs 100%). The addition of 10 nM hydrocortisone to 1,25(OH)₂D₃ produced a significant decrease in B_max (from 100.2 ± 13.2 to 44 ± 5.6), with mRNA levels similar to those of basal conditions (116 ± 25% vs 100%). However, the addition of 10 nM deflazacort did not reduce the activation in B_max produced by 1,25(OH)₂D₃ (92.4 ± 16 vs 100.2 ± 13.2), maintaining the increase in mRNA levels (430 ± 10% vs 483 ± 170%). If 10 nM hydrocortisone or 10 nM deflazacort was added to UMR-106 cells without 1,25(OH)₂D₃, a similar increase was observed in B_max with respect to basal conditions (20.4 ± 1.3 or 20.9 ± 1.6 vs 11.4 ± 4.8 in control cells), but hydrocortisone did not produce any significant variation in mRNA VDR levels, while deflazacort itself produced an increase in VDR mRNA expression.

Conclusion. Our findings of different actions produced by hydrocortisone and deflazacort on the increase of VDR levels produced by 1,25(OH)₂D₃ could explain some of the different actions produced by both antiinflammatory medications on bone metabolism. (J Rheumatol 2004;31:167-72)

Key Indexing Terms:

CORTISOL
DEFLAZACORT
1,25-DIHYDROXYVITAMIN D
VITAMIN D RECEPTOR
VITAMIN D RECEPTOR mRNA

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From the Biochemistry Laboratory, Bone Pathophysiology Section, and Immunology Section, Fundación Jiménez Díaz, Madrid, Spain.

Supported by a grant from the Spanish Institute of Health (FIS 95/1199).

R. Guerrero, PhD, Research Fellow; C. de la Piedra, PhD, Associate Head, Biochemistry Laboratory; E. Teixeiro, PhD, Research Fellow; R. Bragado, PhD, Associate Head, Immunology Section; M.L. Traba, PhD, Associate Head, Biochemistry Laboratory.

Address reprint requests to Dr. M.L. Traba, Fundación Jiménez Díaz, Lab. Bioquímica, Sección de Fisiopatología Ósea, Avda Reyes Católicos 2, 28040 Madrid, Spain. E-mail: mltraba@fjd.es

Submitted May 21, 2002; revision accepted July 21, 2003.

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