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Biphasic regulation of chondrocytes by Rela through induction of anti-apoptotic and catabolic target genes
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 ch...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5109547/ https://www.ncbi.nlm.nih.gov/pubmed/27830706 http://dx.doi.org/10.1038/ncomms13336 |
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author | Kobayashi, Hiroshi Chang, Song Ho Mori, Daisuke Itoh, Shozo Hirata, Makoto Hosaka, Yoko Taniguchi, Yuki Okada, Keita Mori, Yoshifumi Yano, Fumiko Chung, Ung-il Akiyama, Haruhiko Kawaguchi, Hiroshi Tanaka, Sakae Saito, Taku |
author_facet | Kobayashi, Hiroshi Chang, Song Ho Mori, Daisuke Itoh, Shozo Hirata, Makoto Hosaka, Yoko Taniguchi, Yuki Okada, Keita Mori, Yoshifumi Yano, Fumiko Chung, Ung-il Akiyama, Haruhiko Kawaguchi, Hiroshi Tanaka, Sakae Saito, Taku |
author_sort | Kobayashi, Hiroshi |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5109547 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-51095472017-01-13 Biphasic regulation of chondrocytes by Rela through induction of anti-apoptotic and catabolic target genes Kobayashi, Hiroshi Chang, Song Ho Mori, Daisuke Itoh, Shozo Hirata, Makoto Hosaka, Yoko Taniguchi, Yuki Okada, Keita Mori, Yoshifumi Yano, Fumiko Chung, Ung-il Akiyama, Haruhiko Kawaguchi, Hiroshi Tanaka, Sakae Saito, Taku Nat Commun Article 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. Nature Publishing Group 2016-11-10 /pmc/articles/PMC5109547/ /pubmed/27830706 http://dx.doi.org/10.1038/ncomms13336 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Kobayashi, Hiroshi Chang, Song Ho Mori, Daisuke Itoh, Shozo Hirata, Makoto Hosaka, Yoko Taniguchi, Yuki Okada, Keita Mori, Yoshifumi Yano, Fumiko Chung, Ung-il Akiyama, Haruhiko Kawaguchi, Hiroshi Tanaka, Sakae Saito, Taku Biphasic regulation of chondrocytes by Rela through induction of anti-apoptotic and catabolic target genes |
title | Biphasic regulation of chondrocytes by Rela through induction of anti-apoptotic and catabolic target genes |
title_full | Biphasic regulation of chondrocytes by Rela through induction of anti-apoptotic and catabolic target genes |
title_fullStr | Biphasic regulation of chondrocytes by Rela through induction of anti-apoptotic and catabolic target genes |
title_full_unstemmed | Biphasic regulation of chondrocytes by Rela through induction of anti-apoptotic and catabolic target genes |
title_short | Biphasic regulation of chondrocytes by Rela through induction of anti-apoptotic and catabolic target genes |
title_sort | biphasic regulation of chondrocytes by rela through induction of anti-apoptotic and catabolic target genes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5109547/ https://www.ncbi.nlm.nih.gov/pubmed/27830706 http://dx.doi.org/10.1038/ncomms13336 |
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