RRC ID 42660
Author Shin HH, Kim SJ, Kang SY, Lee DS, Choi HS.
Title Soluble glucocorticoid-induced tumor necrosis factor receptor stimulates osteoclastogenesis by down-regulation of osteoprotegerin in bone marrow stromal cells.
Journal Bone
Abstract Soluble glucocorticoid-induced tumor necrosis factor receptor (sGITR) is a potent stimulator of osteoclastogenesis. The mechanism by which it induces osteoclastogenesis was studied by culturing bone-marrow-derived macrophages (BMM) with conditioned medium from mouse bone marrow stromal cells. GITR and GITR ligand (GITRL) were expressed on the surface of bone marrow stromal cells, and sGITR-induced osteoclastogenesis was inhibited by anti-GITRL Ab, indicating that stimulatory effect of osteoclastogenesis by sGITR involved signaling via GITRL. Bone marrow stromal cells up-regulated cyclooxygenase-2 (COX-2) and produced prostaglandin E(2) (PGE(2)) early in their response to sGITR, and the stimulation of osteoclastogenesis was markedly inhibited by NS398, a COX-2 inhibitor. Later, sGITR markedly reduced the steady-state level of osteoprotegerin (OPG) mRNA and increased receptor activator of nuclear factor-kappaB ligand (RANKL) mRNA. NS398 blocked the sGITR-induced reduction of OPG mRNA but did not significantly affect the sGITR-induced rise in RANKL mRNA. This suggests that down-regulation of OPG by PGE(2) is involved in sGITR-induced osteoclast (OC) formation in the presence of conditioned medium from mouse bone marrow stromal cells.
Volume 39(4)
Pages 716-23
Published 2006-10-1
DOI 10.1016/j.bone.2006.03.015
PII S8756-3282(06)00405-4
PMID 16750437
MeSH Animals Antibodies / pharmacology Bone Marrow Cells / cytology Bone Marrow Cells / drug effects Bone Marrow Cells / metabolism* Cell Line Cells, Cultured Cyclooxygenase 2 / genetics Cyclooxygenase 2 / metabolism Cyclooxygenase 2 Inhibitors / pharmacology Dose-Response Relationship, Drug Down-Regulation Flow Cytometry Gene Expression / drug effects Glucocorticoid-Induced TNFR-Related Protein Mice Mice, Inbred C57BL Osteoclasts / cytology Osteoclasts / drug effects Osteoclasts / metabolism Osteoprotegerin / genetics Osteoprotegerin / metabolism* Prostaglandins E / metabolism RANK Ligand / genetics RANK Ligand / metabolism Receptors, Nerve Growth Factor / genetics Receptors, Nerve Growth Factor / immunology Receptors, Nerve Growth Factor / physiology* Receptors, Tumor Necrosis Factor / genetics Receptors, Tumor Necrosis Factor / immunology Receptors, Tumor Necrosis Factor / physiology* Reverse Transcriptase Polymerase Chain Reaction Stromal Cells / cytology Stromal Cells / drug effects Stromal Cells / metabolism* Tumor Necrosis Factors / genetics Tumor Necrosis Factors / physiology
IF 4.147
Times Cited 10
Human and Animal Cells ST2(RCB0224)