論文 - 詳細
| RRC ID | 37921 |
|---|---|
| 著者 | Kim JA, Im S, Cantley LC, Kim DW. |
| タイトル | Suppression of Nkx3.2 by phosphatidylinositol-3-kinase signaling regulates cartilage development by modulating chondrocyte hypertrophy. |
| ジャーナル | Cell Signal |
| Abstract |
Phosphatidylinositol-3-kinase (PI3K) is a key regulator of diverse biological processes including cell proliferation, migration, survival, and differentiation. While a role of PI3K in chondrocyte differentiation has been suggested, its precise mechanisms of action are poorly understood. Here we show that PI3K signaling can down-regulate Nkx3.2 at both mRNA and protein levels in various chondrocyte cultures in vitro. In addition, we have intriguingly found that p85β, not p85α, is specifically employed as a regulatory subunit for PI3K-mediated Nkx3.2 suppression. Furthermore, we found that regulation of Nkx3.2 by PI3K requires Rac1-PAK1, but not Akt, signaling downstream of PI3K. Finally, using embryonic limb bud cultures, ex vivo long bone cultures, and p85β knockout mice, we demonstrated that PI3K-mediated suppression of Nkx3.2 in chondrocytes plays a role in the control of cartilage hypertrophy during skeletal development in vertebrates. |
| 巻・号 | 27(12) |
| ページ | 2389-400 |
| 公開日 | 2015-12-1 |
| DOI | 10.1016/j.cellsig.2015.09.004 |
| PII | S0898-6568(15)00266-1 |
| PMID | 26363466 |
| PMC | PMC4847727 |
| MeSH | Animals Cartilage / pathology Cell Enlargement Cell Proliferation Chondrocytes / physiology* Chondrogenesis Gene Silencing HEK293 Cells Homeodomain Proteins / genetics Homeodomain Proteins / metabolism* Humans Hypertrophy / metabolism Mice Mice, Knockout NIH 3T3 Cells Phosphatidylinositol 3-Kinases / metabolism* RNA, Messenger / genetics RNA, Messenger / metabolism Signal Transduction Transcription Factors / genetics Transcription Factors / metabolism* p21-Activated Kinases / metabolism rac1 GTP-Binding Protein / metabolism |
| IF | 3.968 |
| 引用数 | 6 |
| WOS 分野 | CELL BIOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | ATDC5(RCB0565) |