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Overexpression of Sirtuin 6 suppresses cellular senescence and NF-κB mediated inflammatory responses in osteoarthritis development

The aim of our study was to evaluate if Sirt6, a NAD + dependent histone deacetylase, plays a protective role in cartilage degeneration by suppressing cellular senescence and inflammatory responses. The expression level of sirt6 in normal and OA human knee articular cartilage was compared by immunof...

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Autores principales: Wu, Yaosen, Chen, Linwei, Wang, Ye, Li, Wanli, Lin, Yan, Yu, Dongsheng, Zhang, Liang, Li, Fangcai, Pan, Zhijun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4671011/
https://www.ncbi.nlm.nih.gov/pubmed/26639398
http://dx.doi.org/10.1038/srep17602
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author Wu, Yaosen
Chen, Linwei
Wang, Ye
Li, Wanli
Lin, Yan
Yu, Dongsheng
Zhang, Liang
Li, Fangcai
Pan, Zhijun
author_facet Wu, Yaosen
Chen, Linwei
Wang, Ye
Li, Wanli
Lin, Yan
Yu, Dongsheng
Zhang, Liang
Li, Fangcai
Pan, Zhijun
author_sort Wu, Yaosen
collection PubMed
description The aim of our study was to evaluate if Sirt6, a NAD + dependent histone deacetylase, plays a protective role in cartilage degeneration by suppressing cellular senescence and inflammatory responses. The expression level of sirt6 in normal and OA human knee articular cartilage was compared by immunofluorescence and western blotting. The effect of sirt6 overexpression on replicative senescence of chondrocytes and NF-κB target genes expression was evaluated. Histological assessment of OA mice knee joint was carried out to assess the in vivo effects of sirt6 overexpression on mice chondrocytes. We found sirt6 level was significantly decreased in the articular chondrocytes of OA patients compare to normal human. SA-β-gal staining revealed that overexpression of sirt6 suppressed replicative senescence of chondrocytes. Meanwhile, the expression of NF-κB dependent genes were significantly attenuated by sirt6 overxpression. Safranin-O staining and OARSI score of knee joint cartilage in OA mice revealed that Lenti-Sirt6 intraarticular injection could protect mice chondrocytes from degeneration. These data strongly suggest that overexpression of Sirt6 can prevent OA development by reducing both the inflammatory response and chondrocytes senescence. Therefore, the development of specific activators of Sirt6 may have therapeutic potential for the treatment of OA.
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spelling pubmed-46710112015-12-11 Overexpression of Sirtuin 6 suppresses cellular senescence and NF-κB mediated inflammatory responses in osteoarthritis development Wu, Yaosen Chen, Linwei Wang, Ye Li, Wanli Lin, Yan Yu, Dongsheng Zhang, Liang Li, Fangcai Pan, Zhijun Sci Rep Article The aim of our study was to evaluate if Sirt6, a NAD + dependent histone deacetylase, plays a protective role in cartilage degeneration by suppressing cellular senescence and inflammatory responses. The expression level of sirt6 in normal and OA human knee articular cartilage was compared by immunofluorescence and western blotting. The effect of sirt6 overexpression on replicative senescence of chondrocytes and NF-κB target genes expression was evaluated. Histological assessment of OA mice knee joint was carried out to assess the in vivo effects of sirt6 overexpression on mice chondrocytes. We found sirt6 level was significantly decreased in the articular chondrocytes of OA patients compare to normal human. SA-β-gal staining revealed that overexpression of sirt6 suppressed replicative senescence of chondrocytes. Meanwhile, the expression of NF-κB dependent genes were significantly attenuated by sirt6 overxpression. Safranin-O staining and OARSI score of knee joint cartilage in OA mice revealed that Lenti-Sirt6 intraarticular injection could protect mice chondrocytes from degeneration. These data strongly suggest that overexpression of Sirt6 can prevent OA development by reducing both the inflammatory response and chondrocytes senescence. Therefore, the development of specific activators of Sirt6 may have therapeutic potential for the treatment of OA. Nature Publishing Group 2015-12-07 /pmc/articles/PMC4671011/ /pubmed/26639398 http://dx.doi.org/10.1038/srep17602 Text en Copyright © 2015, Macmillan Publishers Limited 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
Wu, Yaosen
Chen, Linwei
Wang, Ye
Li, Wanli
Lin, Yan
Yu, Dongsheng
Zhang, Liang
Li, Fangcai
Pan, Zhijun
Overexpression of Sirtuin 6 suppresses cellular senescence and NF-κB mediated inflammatory responses in osteoarthritis development
title Overexpression of Sirtuin 6 suppresses cellular senescence and NF-κB mediated inflammatory responses in osteoarthritis development
title_full Overexpression of Sirtuin 6 suppresses cellular senescence and NF-κB mediated inflammatory responses in osteoarthritis development
title_fullStr Overexpression of Sirtuin 6 suppresses cellular senescence and NF-κB mediated inflammatory responses in osteoarthritis development
title_full_unstemmed Overexpression of Sirtuin 6 suppresses cellular senescence and NF-κB mediated inflammatory responses in osteoarthritis development
title_short Overexpression of Sirtuin 6 suppresses cellular senescence and NF-κB mediated inflammatory responses in osteoarthritis development
title_sort overexpression of sirtuin 6 suppresses cellular senescence and nf-κb mediated inflammatory responses in osteoarthritis development
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4671011/
https://www.ncbi.nlm.nih.gov/pubmed/26639398
http://dx.doi.org/10.1038/srep17602
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