RRC ID 51930
Author 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.
Title Biphasic regulation of chondrocytes by Rela through induction of anti-apoptotic and catabolic target genes.
Journal 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.
Volume 7
Pages 13336
Published 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 12.353
Resource
Human and Animal Cells ATDC5(RCB0565)