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

摘要

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 -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.