論文 - 詳細
| RRC ID | 73038 |
|---|---|
| 著者 | Rubin J, Ackert-Bicknell CL, Zhu L, Fan X, Murphy TC, Nanes MS, Marcus R, Holloway L, Beamer WG, Rosen CJ. |
| タイトル | IGF-I regulates osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand in vitro and OPG in vivo. |
| ジャーナル | J Clin Endocrinol Metab |
| Abstract |
IGF-I, a ubiquitous polypeptide, plays a key role in longitudinal bone growth and acquisition. The most predominant effect of skeletal IGF-I is acceleration of the differentiation program for osteoblasts. However, in vivo studies using recombinant human (rh) IGF-I and/or rhGH have demonstrated stimulation of both bone formation and resorption, thereby potentially limiting the usefulness of these peptides in the treatment of osteoporosis. In this study, we hypothesized that IGF-I modulates bone resorption by regulating expression of osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB (RANK) ligand (RANKL) in bone cells. Using Northern analysis in ST2 cells, we found that human IGF-I suppressed OPG mRNA in a time- and dose-dependent manner: 100 micro g/LIGF-I (13 nM) decreased OPG expression by 37.0 +/- 1.8% (P < 0.002). The half maximal inhibitory dose of IGF-I was reached at 50 micro g/liter ( approximately 6.5 nM) with no effect of IGF-I on OPG message stability. Conditioned media from ST2 cells confirmed that IGF-I decreased secreted OPG, reducing levels by 42%, from 12.1-7 ng/ml at 48 h (P < 0.05). Similarly, IGF-I at 100 micro g/liter (13 nM) increased RANKL mRNA expression to 353 +/- 74% above untreated cells as assessed by real-time PCR. In vivo, low doses of rhGH when administered to elderly postmenopausal women only modestly raised serum IGF-I (to concentrations of 18-26 nM) and did not affect circulating OPG concentrations; however, administration of rhIGF-I (30 micro g/kg.d) for 1 yr to older women resulted in a significant increase in serum IGF-I (to concentrations of 39-45 nM) and a 20% reduction in serum OPG (P < 0.05). In summary, we conclude that IGF-I in a dose- and time-dependent manner regulates OPG and RANKL in vitro and in vivo. These data suggest IGF-I may act as a coupling factor in bone remodeling by activating both bone formation and bone resorption; the latter effect appears to be mediated through the OPG/RANKL system in bone. |
| 巻・号 | 87(9) |
| ページ | 4273-9 |
| 公開日 | 2002-9-1 |
| DOI | 10.1210/jc.2002-020656 |
| PMID | 12213884 |
| MeSH | Animals Carrier Proteins / genetics* Cell Line Gene Expression Regulation / drug effects* Glycoproteins / genetics* Human Growth Hormone / pharmacology Humans Insulin-Like Growth Factor I / pharmacology* Kinetics Membrane Glycoproteins / genetics* Mice NF-kappa B / metabolism Osteoprotegerin RANK Ligand RNA, Messenger / genetics Receptor Activator of Nuclear Factor-kappa B Receptors, Cytoplasmic and Nuclear / genetics* Receptors, Tumor Necrosis Factor Recombinant Proteins / pharmacology Stromal Cells / cytology Transcription, Genetic* / drug effects |
| IF | 5.399 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | ST2(RCB0224) |