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Inhibition of HDAC6 by Tubastatin A reduces chondrocyte oxidative stress in chondrocytes and ameliorates mouse osteoarthritis by activating autophagy

The aim of this study was to determine the effect of HDAC6 inhibition using the selective inhibitor Tubastatin A (TubA) on the regulation of tert-butyl hydroperoxide (TBHP)-treated chondrocytes and a mouse OA model. Using conventional molecular biology methods, our results showed that the level of H...

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Autores principales: Shen, Zhonghai, Ji, Kang, Cai, Zhenhai, Huang, Chenglong, He, Xiaojun, Xu, Hongwei, Chen, Gang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064156/
https://www.ncbi.nlm.nih.gov/pubmed/33744850
http://dx.doi.org/10.18632/aging.202736
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author Shen, Zhonghai
Ji, Kang
Cai, Zhenhai
Huang, Chenglong
He, Xiaojun
Xu, Hongwei
Chen, Gang
author_facet Shen, Zhonghai
Ji, Kang
Cai, Zhenhai
Huang, Chenglong
He, Xiaojun
Xu, Hongwei
Chen, Gang
author_sort Shen, Zhonghai
collection PubMed
description The aim of this study was to determine the effect of HDAC6 inhibition using the selective inhibitor Tubastatin A (TubA) on the regulation of tert-butyl hydroperoxide (TBHP)-treated chondrocytes and a mouse OA model. Using conventional molecular biology methods, our results showed that the level of HDAC6 increases both in the cartilage of osteoarthritis (OA) mice and TBHP-treated chondrocytes in vitro. TubA treatment effectively inhibits the expression of HDAC6, attenuates oxidative stress, reduces the level of apoptotic proteins to maintain chondrocyte survival, and suppresses the extracellular matrix (ECM) degradation. In addition, our results also revealed that HDAC6 inhibition by TubA activates autophagy in chondrocytes, whereas the protective effects of TubA were abolished by autophagy inhibitor intervention. Subsequently, the positive effects of HDAC6 inhibition by TubA were also found in a mouse OA model. Therefore, our study provide evidence that HDAC6 inhibition prevents OA development, and HDAC6 could be applied as a potential therapeutic target for OA management.
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spelling pubmed-80641562021-04-26 Inhibition of HDAC6 by Tubastatin A reduces chondrocyte oxidative stress in chondrocytes and ameliorates mouse osteoarthritis by activating autophagy Shen, Zhonghai Ji, Kang Cai, Zhenhai Huang, Chenglong He, Xiaojun Xu, Hongwei Chen, Gang Aging (Albany NY) Research Paper The aim of this study was to determine the effect of HDAC6 inhibition using the selective inhibitor Tubastatin A (TubA) on the regulation of tert-butyl hydroperoxide (TBHP)-treated chondrocytes and a mouse OA model. Using conventional molecular biology methods, our results showed that the level of HDAC6 increases both in the cartilage of osteoarthritis (OA) mice and TBHP-treated chondrocytes in vitro. TubA treatment effectively inhibits the expression of HDAC6, attenuates oxidative stress, reduces the level of apoptotic proteins to maintain chondrocyte survival, and suppresses the extracellular matrix (ECM) degradation. In addition, our results also revealed that HDAC6 inhibition by TubA activates autophagy in chondrocytes, whereas the protective effects of TubA were abolished by autophagy inhibitor intervention. Subsequently, the positive effects of HDAC6 inhibition by TubA were also found in a mouse OA model. Therefore, our study provide evidence that HDAC6 inhibition prevents OA development, and HDAC6 could be applied as a potential therapeutic target for OA management. Impact Journals 2021-03-19 /pmc/articles/PMC8064156/ /pubmed/33744850 http://dx.doi.org/10.18632/aging.202736 Text en Copyright: © 2021 Shen et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Shen, Zhonghai
Ji, Kang
Cai, Zhenhai
Huang, Chenglong
He, Xiaojun
Xu, Hongwei
Chen, Gang
Inhibition of HDAC6 by Tubastatin A reduces chondrocyte oxidative stress in chondrocytes and ameliorates mouse osteoarthritis by activating autophagy
title Inhibition of HDAC6 by Tubastatin A reduces chondrocyte oxidative stress in chondrocytes and ameliorates mouse osteoarthritis by activating autophagy
title_full Inhibition of HDAC6 by Tubastatin A reduces chondrocyte oxidative stress in chondrocytes and ameliorates mouse osteoarthritis by activating autophagy
title_fullStr Inhibition of HDAC6 by Tubastatin A reduces chondrocyte oxidative stress in chondrocytes and ameliorates mouse osteoarthritis by activating autophagy
title_full_unstemmed Inhibition of HDAC6 by Tubastatin A reduces chondrocyte oxidative stress in chondrocytes and ameliorates mouse osteoarthritis by activating autophagy
title_short Inhibition of HDAC6 by Tubastatin A reduces chondrocyte oxidative stress in chondrocytes and ameliorates mouse osteoarthritis by activating autophagy
title_sort inhibition of hdac6 by tubastatin a reduces chondrocyte oxidative stress in chondrocytes and ameliorates mouse osteoarthritis by activating autophagy
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064156/
https://www.ncbi.nlm.nih.gov/pubmed/33744850
http://dx.doi.org/10.18632/aging.202736
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