論文 - 詳細
| RRC ID | 51930 |
|---|---|
| 著者 | Kobayashi H, Chang SH, Mori D, Itoh S, Hirata M, Hosaka Y, Taniguchi Y, Okada K, Mori Y, Yano F, Chung UI, Akiyama H, Kawaguchi H, Tanaka S, Saito T. |
| タイトル | Biphasic regulation of chondrocytes by Rela through induction of anti-apoptotic and catabolic target genes. |
| ジャーナル | Nat Commun |
| Abstract |
In vitro studies have shown that Rela/p65, a key subunit mediating NF-κB signalling, is involved in chondrogenic differentiation, cell survival and catabolic enzyme production. Here, we analyse in vivo functions of Rela in embryonic limbs and adult articular cartilage, and find that Rela protects chondrocytes from apoptosis through induction of anti-apoptotic genes including Pik3r1. During skeletal development, homozygous knockout of Rela leads to impaired growth through enhanced chondrocyte apoptosis, whereas heterozygous knockout of Rela does not alter growth. In articular cartilage, homozygous knockout of Rela at 7 weeks leads to marked acceleration of osteoarthritis through enhanced chondrocyte apoptosis, whereas heterozygous knockout of Rela results in suppression of osteoarthritis development through inhibition of catabolic gene expression. Haploinsufficiency or a low dose of an IKK inhibitor suppresses catabolic gene expression, but does not alter anti-apoptotic gene expression. The biphasic regulation of chondrocytes by Rela contributes to understanding the pathophysiology of osteoarthritis. |
| 巻・号 | 7 |
| ページ | 13336 |
| 公開日 | 2016-11-10 |
| DOI | 10.1038/ncomms13336 |
| PII | ncomms13336 |
| PMID | 27830706 |
| PMC | PMC5109547 |
| MeSH | Animals Animals, Newborn Apoptosis / genetics* Cell Differentiation / genetics Cell Line, Tumor Cells, Cultured Chondrocytes / metabolism* Chondrogenesis / genetics Gene Expression Profiling / methods* Humans Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Osteoarthritis / genetics Osteoarthritis / metabolism Transcription Factor RelA / genetics* Transcription Factor RelA / metabolism |
| IF | 12.121 |
| 引用数 | 29 |
| 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 | X(Twitter) |
| 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 | ATDC5(RCB0565) |