RRC ID |
42660
|
著者 |
Shin HH, Kim SJ, Kang SY, Lee DS, Choi HS.
|
タイトル |
Soluble glucocorticoid-induced tumor necrosis factor receptor stimulates osteoclastogenesis by down-regulation of osteoprotegerin in bone marrow stromal cells.
|
ジャーナル |
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.
|
巻・号 |
39(4)
|
ページ |
716-23
|
公開日 |
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
|
引用数 |
10
|
WOS 分野
|
ENDOCRINOLOGY & METABOLISM
|
リソース情報 |
ヒト・動物細胞 |
ST2(RCB0224) |