論文 - 詳細
| RRC ID | 42161 |
|---|---|
| 著者 | Karst M, Gorny G, Galvin RJ, Oursler MJ. |
| タイトル | Roles of stromal cell RANKL, OPG, and M-CSF expression in biphasic TGF-beta regulation of osteoclast differentiation. |
| ジャーナル | J Cell Physiol |
| Abstract |
To better understand the complex roles of transforming growth factor-beta (TGF-beta) in bone metabolism, we examined the impact of a range of TGF-beta concentrations on osteoclast differentiation. In co-cultures of support cells and spleen or marrow osteoclast precursors, low TGF-beta concentrations stimulated while high concentrations inhibited differentiation. We investigated the influences of TGF-beta on macrophage colony stimulating factor (M-CSF), receptor activator of NF-kappaB ligand (RANKL), and osteoprotegerin (OPG) expression and found a dose dependent inhibition of M-CSF expression. RANKL expression was elevated at low TGF-beta concentrations with a less dramatic increase in OPG. Addition of OPG blocked differentiation at the stimulatory TGF-beta dose. Thus, low TGF-beta concentrations elevated the RANKL/OPG ratio while high concentrations did not, supporting that, at low TGF-beta concentrations, there is sufficient M-CSF and a high RANKL/OPG ratio to stimulate differentiation. At high TGF-beta concentrations, the RANKL/OPG ratio and M-CSF expression were both repressed and there was no differentiation. We examined whether TGF-beta-mediated repression of osteoclasts differentiation is due to these changes by adding M-CSF and/or RANKL and did not observe any impact on differentiation repression. We studied direct TGF-beta impacts on osteoclast precursors by culturing spleen or marrow cells with M-CSF and RANKL. TGF-beta treatment dose-dependently stimulated osteoclast differentiation. These data indicate that low TGF-beta levels stimulate osteoclast differentiation by impacting the RANKL/OPG ratio while high TGF-beta levels repress osteoclast differentiation by multiple avenues including mechanisms independent of the RANKL/OPG ratio or M-CSF expression regulation. |
| 巻・号 | 200(1) |
| ページ | 99-106 |
| 公開日 | 2004-7-1 |
| DOI | 10.1002/jcp.20036 |
| PMID | 15137062 |
| PMC | PMC4547836 |
| MeSH | Animals Bone Marrow Cells / cytology Carrier Proteins / metabolism* Cell Differentiation* Cells, Cultured Coculture Techniques Dose-Response Relationship, Drug Female Gene Expression Regulation Glycoproteins / metabolism* Macrophage Colony-Stimulating Factor / metabolism* Membrane Glycoproteins / metabolism* Mice Mice, Inbred BALB C Osteoclasts / cytology* Osteoclasts / drug effects Osteoprotegerin RANK Ligand Receptor Activator of Nuclear Factor-kappa B Receptors, Cytoplasmic and Nuclear / metabolism* Receptors, Tumor Necrosis Factor Spleen / cytology Stromal Cells / cytology Stromal Cells / metabolism Transforming Growth Factor beta / metabolism* Transforming Growth Factor beta / pharmacology Transforming Growth Factor beta1 Transforming Growth Factor beta2 |
| IF | 5.546 |
| 引用数 | 102 |
| WOS 分野 | PHYSIOLOGY CELL BIOLOGY |
| 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) |