J Korean Med Sci.  2001 Dec;16(6):769-773. 10.3346/jkms.2001.16.6.769.

Deflazacort Increases Osteoclast Formation in Mouse Bone Marrow Culture and the Ratio of RANKL/OPG mRNA Expression in Marrow Stromal Cells

• Chung H
• Kang YS
• Hwang CS
• Moon IK
• Yim CH
• Choi KH
• Han KO
• Jang HC
• Yoon HK
• Han IK

• KMID: 648360
• DOI: http://doi.org/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.

Keyword

Glucocorticoids; Osteoclasts; OPG; RANKL

MeSH Terms

Animal
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, Synthetic/pharmacology
Glycoproteins/*genetics
Immunosuppressive Agents/*pharmacology
Male
Membrane Glycoproteins/*genetics
Mice
Mice, Inbred ICR
Osteoclasts/*cytology
Pregnenediones/*pharmacology
RNA, Messenger/analysis
Receptors, Cytoplasmic and Nuclear/*genetics
Stromal Cells/cytology