Deflazacort increases osteoclast formation in mouse bone marrow culture and the ratio of RANKL/OPG mRNA expression in marrow stromal cells

J Korean Med Sci. 2001 Dec;16(6):769-73. doi: 10.3346/jkms.2001.16.6.769.

Abstract

Information on precise effects of deflazacort on bone cell function, especially osteoclasts, is quite limited. Therefore, the present study was undertaken to test effects of deflazacort on osteoclast-like cell formation in mouse bone marrow cultures and on the regulation of osteoprotegerin (OPG) and its ligand (RANKL) mRNA expressions by RT-PCR in the ST2 marrow stromal cells. TRAP-positive mononuclear cells increased after the treatment of deflazacort at 10(-9) to 10(-7) M alone for 6 days in a dose-dependent manner. Number of TRAP-positive multi-nucleated cells (MNCs) increased significantly with combined treatment of deflazacort at 10(-7) M and 1,25-(OH)2D3 at 10(-9) M compared to that of cultures treated with 1,25-(OH)2D3 alone (p<0.05). Exposure to deflazacort at 10(-7) M in the presence of 1,25-(OH)2D3 at 10(-9) M in the last 3-day culture had greater stimulatory effect on osteoclast-like cell formation than that of the first 3-day culture did. Deflazacort at 10(-10) -10(-6) M downregulated OPG and upregulated RANKL in mRNA levels in a dose-dependent manner. These observations suggest that deflazacort stimulate osteoclast precursor in the absence of 1,25-(OH)2D3 and enhance differentiation of osteoclasts in the presence of 1,25-(OH)2D3. These effects are, in part, thought to be mediated by the regulation of the expression of OPG and RANKL mRNA in marrow stromal cells.

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology*
  • Calcitriol / pharmacology
  • Calcium Channel Agonists / pharmacology
  • Carrier Proteins / genetics*
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Dexamethasone / pharmacology
  • Gene Expression / drug effects
  • Glucocorticoids / pharmacology
  • Glycoproteins / genetics*
  • Immunosuppressive Agents / pharmacology*
  • Male
  • Membrane Glycoproteins / genetics*
  • Mice
  • Mice, Inbred ICR
  • Osteoclasts / cytology*
  • Osteoprotegerin
  • Pregnenediones / pharmacology*
  • RANK Ligand
  • RNA, Messenger / analysis
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Receptors, Tumor Necrosis Factor
  • Stromal Cells / cytology

Substances

  • Calcium Channel Agonists
  • Carrier Proteins
  • Glucocorticoids
  • Glycoproteins
  • Immunosuppressive Agents
  • Membrane Glycoproteins
  • Osteoprotegerin
  • Pregnenediones
  • RANK Ligand
  • RNA, Messenger
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Tumor Necrosis Factor
  • Tnfrsf11a protein, mouse
  • Tnfrsf11b protein, mouse
  • Tnfsf11 protein, mouse
  • Dexamethasone
  • Calcitriol
  • deflazacort