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
|
リソース情報 |
ヒト・動物細胞 |
ATDC5(RCB0565) |