title: Deflazacort increases osteoclast formation in mouse bone marrow culture and the ratio of RANKL/OPG mRNA expression in marrow stromal cells.
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.
authors.affiliation: Department of Medicine, Sungkyunkwan University School of Medicine, Samsung Cheil Hospital, Seoul, Korea. chy1009@samsung.co.kr
authors.forename: H
authors.initials: H
authors.lastname: Chung
authors.forename: Y S
authors.initials: YS
authors.lastname: Kang
authors.forename: C S
authors.initials: CS
authors.lastname: Hwang
authors.forename: I K
authors.initials: IK
authors.lastname: Moon
authors.forename: C H
authors.initials: CH
authors.lastname: Yim
authors.forename: K H
authors.initials: KH
authors.lastname: Choi
authors.forename: K O
authors.initials: KO
authors.lastname: Han
authors.forename: H C
authors.initials: HC
authors.lastname: Jang
authors.forename: H K
authors.initials: HK
authors.lastname: Yoon
authors.forename: I K
authors.initials: IK
authors.lastname: Han
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002117:Calcitriol / Q000494:pharmacology; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D006023:Glycoproteins / Q000235:genetics*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008813:Mice, Inbred ICR; D010010:Osteoclasts / Q000166:cytology*; D053244:Osteoprotegerin; D011282:Pregnenediones / Q000494:pharmacology*; D053245:RANK Ligand; D012333:RNA, Messenger / Q000032:analysis; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D018124:Receptors, Tumor Necrosis Factor; D017154:Stromal Cells / Q000166:cytology
chemical_list: D002120:Calcium Channel Agonists; D002352:Carrier Proteins; D005938:Glucocorticoids; D006023:Glycoproteins; D007166:Immunosuppressive Agents; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D011282:Pregnenediones; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D003907:Dexamethasone; D002117:Calcitriol; C021988:deflazacort