1.Deflazacort Increases Osteoclast Formation in Mouse Bone Marrow Culture and the Ratio of RANKL/OPG mRNA Expression in Marrow Stromal Cells.
Hoyeon CHUNG ; Young Soon KANG ; Chang Sun HWANG ; In Kul MOON ; Chang Hoon YIM ; Kyu Hong CHOI ; Ki Ok HAN ; Hak Chul JANG ; Hyun Koo YOON ; In Kwon HAN
Journal of Korean Medical Science 2001;16(6):769-773
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.
Animal
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Bone Marrow Cells/*cytology
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Calcitriol/pharmacology
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Calcium Channel Agonists/pharmacology
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Carrier Proteins/*genetics
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Cell Differentiation/drug effects
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Cells, Cultured
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Dexamethasone/pharmacology
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Gene Expression/drug effects
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Glucocorticoids, Synthetic/pharmacology
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Glycoproteins/*genetics
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Immunosuppressive Agents/*pharmacology
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Male
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Membrane Glycoproteins/*genetics
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Mice
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Mice, Inbred ICR
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Osteoclasts/*cytology
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Pregnenediones/*pharmacology
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RNA, Messenger/analysis
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Receptors, Cytoplasmic and Nuclear/*genetics
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Stromal Cells/cytology