| RRC ID |
39139
|
| 著者 |
Takai H, Kanematsu M, Yano K, Tsuda E, Higashio K, Ikeda K, Watanabe K, Yamada Y.
|
| タイトル |
Transforming growth factor-beta stimulates the production of osteoprotegerin/osteoclastogenesis inhibitory factor by bone marrow stromal cells.
|
| ジャーナル |
J Biol Chem
|
| Abstract |
Osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor (OCIF) is a recently identified cytokine that belongs to the tumor necrosis factor receptor superfamily and regulates bone mass by inhibiting osteoclastic bone resorption. The present study was undertaken to determine whether OPG/OCIF is produced in bone microenvironment and how the expression is regulated. A transcript for OPG/OCIF at 3.1 kilobases was detected in bone marrow stromal cells (ST2 and MC3T3-G2/PA6) as well as in osteoblastic cells (MC3T3-E1). Transforming growth factor-beta1 (TGF-beta1) markedly increased the steady-state level of OPG/OCIF mRNA in a dose-dependent manner, while TGF-beta1 suppressed the mRNA expression of tumor necrosis factor-related activation-induced cytokine (TRANCE)/receptor activator of NF-kappaB ligand (RANKL), a positive regulator of osteoclastogenesis to which OPG/OCIF binds. The effect of TGF-beta1 on the expression of OPG/OCIF mRNA was transient, with a peak level at 3-6 h. The up-regulation of OPG/OCIF mRNA by TGF-beta1 in ST2 cells did not require de novo protein synthesis and involved both a transcriptional and a post-transcriptional mechanism. Western blot analysis and an enzyme-linked immunosorbent assay revealed that TGF-beta1 significantly increased the secretion of OPG/OCIF protein by ST2 cells at 6-24 h. In murine bone marrow cultures, TGF-beta1 markedly inhibited the formation of tartrate-resistant acid phosphatase-positive multinucleated osteoclast-like cells in the presence of 1,25-dihydroxyvitamin D3, whose effect was significantly reversed by a neutralizing antibody against OPG/OCIF. These results suggest that TGF-beta1 negatively regulates osteoclastogenesis, at least in part, through the induction of OPG/OCIF by bone marrow stromal cells and that the balance between OPG/OCIF and TRANCE/RANKL in local environment may be an important determinant of osteoclastic bone resorption.
|
| 巻・号 |
273(42)
|
| ページ |
27091-6
|
| 公開日 |
1998-10-16
|
| DOI |
10.1074/jbc.273.42.27091
|
| PII |
S0021-9258(19)59642-9
|
| PMID |
9765225
|
| MeSH |
Animals
Bone Marrow Cells / drug effects*
Cell Differentiation
Cell Line
Dose-Response Relationship, Drug
Gene Expression Regulation
Glycoproteins / biosynthesis*
Glycoproteins / genetics
Mice
Models, Biological
Osteoclasts / cytology*
Osteoprotegerin
RNA, Messenger / biosynthesis
Receptors, Cytoplasmic and Nuclear*
Receptors, Tumor Necrosis Factor / biosynthesis*
Stromal Cells / drug effects*
Transforming Growth Factor beta / pharmacology*
|
| IF |
4.238
|
| 引用数 |
239
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
ST2(RCB0224) |
