A positive feedback loop between EZH2 and NOX4 regulates nucleus pulposus cell senescence in age-related intervertebral disc degeneration

BACKGROUND: The senescence of nucleus pulposus (NP) cells plays a vital role in the pathogenesis of intervertebral disc (IVD) degeneration (IDD). NADPH oxidase 4 (NOX4)-associated oxidative stress has been shown to induce premature NP cell senescence. Enhancer of zeste homolog 2 (EZH2) is a crucial...

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Autores principales: Liu, Chang, Liu, Libangxi, Yang, Minghui, Li, Bin, Yi, Jiarong, Ai, Xuezheng, Zhang, Yang, Huang, Bo, Li, Changqing, Feng, Chencheng, Zhou, Yue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Research
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995653/
https://www.ncbi.nlm.nih.gov/pubmed/32025238
http://dx.doi.org/10.1186/s13008-020-0060-x
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author Liu, Chang
Liu, Libangxi
Yang, Minghui
Li, Bin
Yi, Jiarong
Ai, Xuezheng
Zhang, Yang
Huang, Bo
Li, Changqing
Feng, Chencheng
Zhou, Yue
author_facet Liu, Chang
Liu, Libangxi
Yang, Minghui
Li, Bin
Yi, Jiarong
Ai, Xuezheng
Zhang, Yang
Huang, Bo
Li, Changqing
Feng, Chencheng
Zhou, Yue
author_sort Liu, Chang
collection PubMed
description BACKGROUND: The senescence of nucleus pulposus (NP) cells plays a vital role in the pathogenesis of intervertebral disc (IVD) degeneration (IDD). NADPH oxidase 4 (NOX4)-associated oxidative stress has been shown to induce premature NP cell senescence. Enhancer of zeste homolog 2 (EZH2) is a crucial gene regulating cell senescence. The aim of this study was to investigate the roles of EZH2 in NOX4-induced NP cell senescence and a feedback loop between EZH2 and NOX4. RESULTS: The down-regulation of EZH2 and the up-regulation of NOX4 and p16 were observed in the degenerative discs of aging rats. EZH2 regulated NP cell senescence via the H3K27me3-p16 pathway. Also, EZH2 regulated the expression of NOX4 in NP cells through the histone H3 lysine 27 trimethylation (H3K27me3) in the promoter of NOX4 gene. Furthermore, NOX4 down-regulated EZH2 expression in NP cells via the canonical Wnt/β-catenin pathway. CONCLUSIONS: A positive feedback loop between EZH2 and NOX4 is involved in regulating NP cell senescence, which provides a novel insight into the mechanism of IDD and a potential therapeutic target for IDD.
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spelling pubmed-69956532020-02-05 A positive feedback loop between EZH2 and NOX4 regulates nucleus pulposus cell senescence in age-related intervertebral disc degeneration Liu, Chang Liu, Libangxi Yang, Minghui Li, Bin Yi, Jiarong Ai, Xuezheng Zhang, Yang Huang, Bo Li, Changqing Feng, Chencheng Zhou, Yue Cell Div Research BACKGROUND: The senescence of nucleus pulposus (NP) cells plays a vital role in the pathogenesis of intervertebral disc (IVD) degeneration (IDD). NADPH oxidase 4 (NOX4)-associated oxidative stress has been shown to induce premature NP cell senescence. Enhancer of zeste homolog 2 (EZH2) is a crucial gene regulating cell senescence. The aim of this study was to investigate the roles of EZH2 in NOX4-induced NP cell senescence and a feedback loop between EZH2 and NOX4. RESULTS: The down-regulation of EZH2 and the up-regulation of NOX4 and p16 were observed in the degenerative discs of aging rats. EZH2 regulated NP cell senescence via the H3K27me3-p16 pathway. Also, EZH2 regulated the expression of NOX4 in NP cells through the histone H3 lysine 27 trimethylation (H3K27me3) in the promoter of NOX4 gene. Furthermore, NOX4 down-regulated EZH2 expression in NP cells via the canonical Wnt/β-catenin pathway. CONCLUSIONS: A positive feedback loop between EZH2 and NOX4 is involved in regulating NP cell senescence, which provides a novel insight into the mechanism of IDD and a potential therapeutic target for IDD. BioMed Central 2020-02-01 /pmc/articles/PMC6995653/ /pubmed/32025238 http://dx.doi.org/10.1186/s13008-020-0060-x Text en © The Author(s) 2020 Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Liu, Chang
Liu, Libangxi
Yang, Minghui
Li, Bin
Yi, Jiarong
Ai, Xuezheng
Zhang, Yang
Huang, Bo
Li, Changqing
Feng, Chencheng
Zhou, Yue
A positive feedback loop between EZH2 and NOX4 regulates nucleus pulposus cell senescence in age-related intervertebral disc degeneration
title A positive feedback loop between EZH2 and NOX4 regulates nucleus pulposus cell senescence in age-related intervertebral disc degeneration
title_full A positive feedback loop between EZH2 and NOX4 regulates nucleus pulposus cell senescence in age-related intervertebral disc degeneration
title_fullStr A positive feedback loop between EZH2 and NOX4 regulates nucleus pulposus cell senescence in age-related intervertebral disc degeneration
title_full_unstemmed A positive feedback loop between EZH2 and NOX4 regulates nucleus pulposus cell senescence in age-related intervertebral disc degeneration
title_short A positive feedback loop between EZH2 and NOX4 regulates nucleus pulposus cell senescence in age-related intervertebral disc degeneration
title_sort positive feedback loop between ezh2 and nox4 regulates nucleus pulposus cell senescence in age-related intervertebral disc degeneration
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995653/
https://www.ncbi.nlm.nih.gov/pubmed/32025238
http://dx.doi.org/10.1186/s13008-020-0060-x
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