Cargando…

Sirt6 overexpression suppresses senescence and apoptosis of nucleus pulposus cells by inducing autophagy in a model of intervertebral disc degeneration

Treatment of intervertebral disc degeneration (IDD) seeks to prevent senescence and death of nucleus pulposus (NP) cells. Previous studies have shown that sirt6 exerts potent anti-senescent and anti-apoptotic effects in models of age-related degenerative disease. However, it is not known whether sir...

Descripción completa

Detalles Bibliográficos
Autores principales: Chen, Jian, Xie, Jun-Jun, Jin, Meng-Yun, Gu, Yun-Tao, Wu, Cong-Cong, Guo, Wei-Jun, Yan, Ying-Zhao, Zhang, Zeng-Jie, Wang, Jian-Le, Zhang, Xiao-Lei, Lin, Yan, Sun, Jia-Li, Zhu, Guang-Hui, Wang, Xiang-Yang, Wu, Yao-Sen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833741/
https://www.ncbi.nlm.nih.gov/pubmed/29352194
http://dx.doi.org/10.1038/s41419-017-0085-5
_version_ 1783303525345787904
author Chen, Jian
Xie, Jun-Jun
Jin, Meng-Yun
Gu, Yun-Tao
Wu, Cong-Cong
Guo, Wei-Jun
Yan, Ying-Zhao
Zhang, Zeng-Jie
Wang, Jian-Le
Zhang, Xiao-Lei
Lin, Yan
Sun, Jia-Li
Zhu, Guang-Hui
Wang, Xiang-Yang
Wu, Yao-Sen
author_facet Chen, Jian
Xie, Jun-Jun
Jin, Meng-Yun
Gu, Yun-Tao
Wu, Cong-Cong
Guo, Wei-Jun
Yan, Ying-Zhao
Zhang, Zeng-Jie
Wang, Jian-Le
Zhang, Xiao-Lei
Lin, Yan
Sun, Jia-Li
Zhu, Guang-Hui
Wang, Xiang-Yang
Wu, Yao-Sen
author_sort Chen, Jian
collection PubMed
description Treatment of intervertebral disc degeneration (IDD) seeks to prevent senescence and death of nucleus pulposus (NP) cells. Previous studies have shown that sirt6 exerts potent anti-senescent and anti-apoptotic effects in models of age-related degenerative disease. However, it is not known whether sirt6 protects against IDD. Here, we explored whether sirt6 influenced IDD. The sirt6 level was reduced in senescent human NP cells. Sirt6 overexpression protected against apoptosis and both replicative and stress-induced premature senescence. Sirt6 also activated NP cell autophagy both in vivo and in vitro. 3-methyladenine (3-MA) and chloroquine (CQ)-mediated inhibition of autophagy partially reversed the anti-senescent and anti-apoptotic effects of sirt6, which regulated the expression of degeneration-associated proteins. In vivo, sirt6 overexpression attenuated IDD. Together, the data showed that sirt6 attenuated cell senescence, and reduced apoptosis, by triggering autophagy that ultimately ameliorated IDD. Thus, sirt6 may be a novel therapeutic target for IDD treatment.
format Online
Article
Text
id pubmed-5833741
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-58337412018-03-06 Sirt6 overexpression suppresses senescence and apoptosis of nucleus pulposus cells by inducing autophagy in a model of intervertebral disc degeneration Chen, Jian Xie, Jun-Jun Jin, Meng-Yun Gu, Yun-Tao Wu, Cong-Cong Guo, Wei-Jun Yan, Ying-Zhao Zhang, Zeng-Jie Wang, Jian-Le Zhang, Xiao-Lei Lin, Yan Sun, Jia-Li Zhu, Guang-Hui Wang, Xiang-Yang Wu, Yao-Sen Cell Death Dis Article Treatment of intervertebral disc degeneration (IDD) seeks to prevent senescence and death of nucleus pulposus (NP) cells. Previous studies have shown that sirt6 exerts potent anti-senescent and anti-apoptotic effects in models of age-related degenerative disease. However, it is not known whether sirt6 protects against IDD. Here, we explored whether sirt6 influenced IDD. The sirt6 level was reduced in senescent human NP cells. Sirt6 overexpression protected against apoptosis and both replicative and stress-induced premature senescence. Sirt6 also activated NP cell autophagy both in vivo and in vitro. 3-methyladenine (3-MA) and chloroquine (CQ)-mediated inhibition of autophagy partially reversed the anti-senescent and anti-apoptotic effects of sirt6, which regulated the expression of degeneration-associated proteins. In vivo, sirt6 overexpression attenuated IDD. Together, the data showed that sirt6 attenuated cell senescence, and reduced apoptosis, by triggering autophagy that ultimately ameliorated IDD. Thus, sirt6 may be a novel therapeutic target for IDD treatment. Nature Publishing Group UK 2018-01-19 /pmc/articles/PMC5833741/ /pubmed/29352194 http://dx.doi.org/10.1038/s41419-017-0085-5 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Chen, Jian
Xie, Jun-Jun
Jin, Meng-Yun
Gu, Yun-Tao
Wu, Cong-Cong
Guo, Wei-Jun
Yan, Ying-Zhao
Zhang, Zeng-Jie
Wang, Jian-Le
Zhang, Xiao-Lei
Lin, Yan
Sun, Jia-Li
Zhu, Guang-Hui
Wang, Xiang-Yang
Wu, Yao-Sen
Sirt6 overexpression suppresses senescence and apoptosis of nucleus pulposus cells by inducing autophagy in a model of intervertebral disc degeneration
title Sirt6 overexpression suppresses senescence and apoptosis of nucleus pulposus cells by inducing autophagy in a model of intervertebral disc degeneration
title_full Sirt6 overexpression suppresses senescence and apoptosis of nucleus pulposus cells by inducing autophagy in a model of intervertebral disc degeneration
title_fullStr Sirt6 overexpression suppresses senescence and apoptosis of nucleus pulposus cells by inducing autophagy in a model of intervertebral disc degeneration
title_full_unstemmed Sirt6 overexpression suppresses senescence and apoptosis of nucleus pulposus cells by inducing autophagy in a model of intervertebral disc degeneration
title_short Sirt6 overexpression suppresses senescence and apoptosis of nucleus pulposus cells by inducing autophagy in a model of intervertebral disc degeneration
title_sort sirt6 overexpression suppresses senescence and apoptosis of nucleus pulposus cells by inducing autophagy in a model of intervertebral disc degeneration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833741/
https://www.ncbi.nlm.nih.gov/pubmed/29352194
http://dx.doi.org/10.1038/s41419-017-0085-5
work_keys_str_mv AT chenjian sirt6overexpressionsuppressessenescenceandapoptosisofnucleuspulposuscellsbyinducingautophagyinamodelofintervertebraldiscdegeneration
AT xiejunjun sirt6overexpressionsuppressessenescenceandapoptosisofnucleuspulposuscellsbyinducingautophagyinamodelofintervertebraldiscdegeneration
AT jinmengyun sirt6overexpressionsuppressessenescenceandapoptosisofnucleuspulposuscellsbyinducingautophagyinamodelofintervertebraldiscdegeneration
AT guyuntao sirt6overexpressionsuppressessenescenceandapoptosisofnucleuspulposuscellsbyinducingautophagyinamodelofintervertebraldiscdegeneration
AT wucongcong sirt6overexpressionsuppressessenescenceandapoptosisofnucleuspulposuscellsbyinducingautophagyinamodelofintervertebraldiscdegeneration
AT guoweijun sirt6overexpressionsuppressessenescenceandapoptosisofnucleuspulposuscellsbyinducingautophagyinamodelofintervertebraldiscdegeneration
AT yanyingzhao sirt6overexpressionsuppressessenescenceandapoptosisofnucleuspulposuscellsbyinducingautophagyinamodelofintervertebraldiscdegeneration
AT zhangzengjie sirt6overexpressionsuppressessenescenceandapoptosisofnucleuspulposuscellsbyinducingautophagyinamodelofintervertebraldiscdegeneration
AT wangjianle sirt6overexpressionsuppressessenescenceandapoptosisofnucleuspulposuscellsbyinducingautophagyinamodelofintervertebraldiscdegeneration
AT zhangxiaolei sirt6overexpressionsuppressessenescenceandapoptosisofnucleuspulposuscellsbyinducingautophagyinamodelofintervertebraldiscdegeneration
AT linyan sirt6overexpressionsuppressessenescenceandapoptosisofnucleuspulposuscellsbyinducingautophagyinamodelofintervertebraldiscdegeneration
AT sunjiali sirt6overexpressionsuppressessenescenceandapoptosisofnucleuspulposuscellsbyinducingautophagyinamodelofintervertebraldiscdegeneration
AT zhuguanghui sirt6overexpressionsuppressessenescenceandapoptosisofnucleuspulposuscellsbyinducingautophagyinamodelofintervertebraldiscdegeneration
AT wangxiangyang sirt6overexpressionsuppressessenescenceandapoptosisofnucleuspulposuscellsbyinducingautophagyinamodelofintervertebraldiscdegeneration
AT wuyaosen sirt6overexpressionsuppressessenescenceandapoptosisofnucleuspulposuscellsbyinducingautophagyinamodelofintervertebraldiscdegeneration