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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
42
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pubmed:dateCreated |
1998-11-6
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pubmed:abstractText |
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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Osteoprotegerin,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Tnfrsf11b protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
16
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pubmed:volume |
273
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
27091-6
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:9765225-Animals,
pubmed-meshheading:9765225-Bone Marrow Cells,
pubmed-meshheading:9765225-Cell Differentiation,
pubmed-meshheading:9765225-Cell Line,
pubmed-meshheading:9765225-Dose-Response Relationship, Drug,
pubmed-meshheading:9765225-Gene Expression Regulation,
pubmed-meshheading:9765225-Glycoproteins,
pubmed-meshheading:9765225-Mice,
pubmed-meshheading:9765225-Models, Biological,
pubmed-meshheading:9765225-Osteoclasts,
pubmed-meshheading:9765225-Osteoprotegerin,
pubmed-meshheading:9765225-RNA, Messenger,
pubmed-meshheading:9765225-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:9765225-Receptors, Tumor Necrosis Factor,
pubmed-meshheading:9765225-Stromal Cells,
pubmed-meshheading:9765225-Transforming Growth Factor beta
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pubmed:year |
1998
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pubmed:articleTitle |
Transforming growth factor-beta stimulates the production of osteoprotegerin/osteoclastogenesis inhibitory factor by bone marrow stromal cells.
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pubmed:affiliation |
Department of Geriatric Research, National Institute for Longevity Sciences, Obu, Aichi 474-8522, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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