Deflazacort increases osteoclast formation in mouse bone marrow culture and the ratio of RANKL/OPG mRNA expression in marrow stromal cells.
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.
Chung
H
H
Department of Medicine, Sungkyunkwan University School of Medicine, Samsung Cheil Hospital, Seoul, Korea. chy1009@samsung.co.kr
Kang
Y S
YS
Hwang
C S
CS
Moon
I K
IK
Yim
C H
CH
Choi
K H
KH
Han
K O
KO
Jang
H C
HC
Yoon
H K
HK
Han
I K
IK
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
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