論文 - 詳細
| RRC ID | 43019 |
|---|---|
| 著者 | Macrae VE, Ahmed SF, Mushtaq T, Farquharson C. |
| タイトル | IGF-I signalling in bone growth: inhibitory actions of dexamethasone and IL-1beta. |
| ジャーナル | Growth Horm IGF Res |
| Abstract |
OBJECTIVE:To determine if glucocorticoids and proinflammatory cytokines inhibit bone growth through a common mechanism involving impaired IGF-I signalling. DESIGN:IGF-I (100 ng/ml), dexamethasone (dex) (10(-6)M) and IL-1beta (10 ng/ml) with inhibitors of the PI3K (LY294002) and Erk 1/2 (PD98059 and UO126) IGF-I pathways (all 10 microM) were studied using the ATDC5 chondrocyte cell line and murine fetal metatarsal cultures. RESULTS:IGF-I stimulated ATDC5 chondrocyte proliferation (322%; P < 0.001 versus control). Addition of PD or LY individually to IGF-I supplemented ATDC5 cultures partially reduced proliferation by 32% (P < 0.001), and 66% (P < 0.001), respectively. PD and LY in combination blocked all IGF-I stimulated ATDC5 proliferation. LY significantly reversed IGF-I stimulatory effects on metatarsal growth (P < 0.001), whereas PD and UO treatment had no effect. IGF-I induced ATDC5 proliferation was further decreased when Dex (24%; P < 0.01) or IL-1beta (33%; P < 0.001) were added to PD but not LY cultures. Metatarsal growth inhibition by LY was unaltered by Dex or IL-1beta addition. CONCLUSIONS:Both the PI3K and Erk 1/2 pathways contributed independently to IGF-I mediated ATDC5 proliferation. However in metatarsal cultures, the Erk 1/2 pathway was not required for IGF-I stimulated growth. Dex and IL-1beta may primarily inhibit IGF-I induced bone growth through the PI3K pathway. |
| 巻・号 | 17(5) |
| ページ | 435-9 |
| 公開日 | 2007-10-1 |
| DOI | 10.1016/j.ghir.2007.05.002 |
| PII | S1096-6374(07)00069-X |
| PMID | 17590365 |
| MeSH | Animals Bone Development / drug effects Bone Development / physiology* Cell Line Chondrocytes / drug effects Chondrocytes / physiology* Dexamethasone / pharmacology* Insulin-Like Growth Factor I / pharmacology Insulin-Like Growth Factor I / physiology* Interleukin-1beta / pharmacology* Metatarsal Bones / drug effects Metatarsal Bones / embryology Mice Organ Culture Techniques Signal Transduction / drug effects Signal Transduction / physiology* |
| IF | 1.618 |
| 引用数 | 35 |
| WOS 分野 | ENDOCRINOLOGY & METABOLISM CELL BIOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | ATDC5(RCB0565) |