DNA methyltransferase 3 beta mediates the methylation of the microRNA-34a promoter and enhances chondrocyte viability in osteoarthritis

Osteoarthritis (OA) is characterized by destruction of articular cartilage with an imbalance between synthesis and degradation of extracellular matrix (ECM). In the current study, we explored the role of microRNA-34a (miR-34a) and the behind epigenetic mechanism in the degradation of ECM in OA. Usin...

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Main Authors:	Shouliang Xiong, Yong Zhao, Tiantong Xu
Format:	article
Language:	EN
Published:	Taylor & Francis Group 2021
Subjects:	dnmt3b microrna-34a mcl1 osteoarthritis pi3k/akt pathway Biotechnology TP248.13-248.65
Online Access:	https://doaj.org/article/eb8b0633d16c4208b9da4a29187208f0
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spelling	oai:doaj.org-article:eb8b0633d16c4208b9da4a29187208f02021-12-01T14:41:00ZDNA methyltransferase 3 beta mediates the methylation of the microRNA-34a promoter and enhances chondrocyte viability in osteoarthritis2165-59792165-598710.1080/21655979.2021.2005308https://doaj.org/article/eb8b0633d16c4208b9da4a29187208f02021-12-01T00:00:00Zhttp://dx.doi.org/10.1080/21655979.2021.2005308https://doaj.org/toc/2165-5979https://doaj.org/toc/2165-5987Osteoarthritis (OA) is characterized by destruction of articular cartilage with an imbalance between synthesis and degradation of extracellular matrix (ECM). In the current study, we explored the role of microRNA-34a (miR-34a) and the behind epigenetic mechanism in the degradation of ECM in OA. Using miRNA-based microarray analysis, we found that miR-34a was overexpressed in cartilage tissues of OA patients relative to patients with acute traumatic amputations. Moreover, its expression was positively correlated with the ECM degradation and inflammation. Mechanistically, miR-34a targeted MCL1, and possible target genes of miR-34a were enriched in the PI3K/AKT pathway. Furthermore, DNMT3B inhibited miR-34a by promoting miR-34a methylation. Functional experiments using CCK-8, flow cytometry, Safranin O staining, RT-qPCR, ELISA, Western blot, and HE staining revealed that miR-34a inhibitor suppressed ECM degradation and inflammatory response of chondrocytes and cartilage tissues. By contrast, downregulation of DNMT3B and MCL1 reversed the repressive effects of miR-34a inhibitor in vitro and in vivo. Altogether, our findings establish that silencing of miR-34a by DNMT3B could effectively reduce chondrocyte ECM degradation and inflammatory response in mice by targeting MCL1 and mediating the downstream PI3K/AKT pathway. This present study revealed that miR-34a knockdown might develop a novel intervention for OA treatment.Shouliang XiongYong ZhaoTiantong XuTaylor & Francis Grouparticlednmt3bmicrorna-34amcl1osteoarthritispi3k/akt pathwayBiotechnologyTP248.13-248.65ENBioengineered, Vol 12, Iss 2, Pp 11138-11155 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	dnmt3b microrna-34a mcl1 osteoarthritis pi3k/akt pathway Biotechnology TP248.13-248.65
spellingShingle	dnmt3b microrna-34a mcl1 osteoarthritis pi3k/akt pathway Biotechnology TP248.13-248.65 Shouliang Xiong Yong Zhao Tiantong Xu DNA methyltransferase 3 beta mediates the methylation of the microRNA-34a promoter and enhances chondrocyte viability in osteoarthritis
description	Osteoarthritis (OA) is characterized by destruction of articular cartilage with an imbalance between synthesis and degradation of extracellular matrix (ECM). In the current study, we explored the role of microRNA-34a (miR-34a) and the behind epigenetic mechanism in the degradation of ECM in OA. Using miRNA-based microarray analysis, we found that miR-34a was overexpressed in cartilage tissues of OA patients relative to patients with acute traumatic amputations. Moreover, its expression was positively correlated with the ECM degradation and inflammation. Mechanistically, miR-34a targeted MCL1, and possible target genes of miR-34a were enriched in the PI3K/AKT pathway. Furthermore, DNMT3B inhibited miR-34a by promoting miR-34a methylation. Functional experiments using CCK-8, flow cytometry, Safranin O staining, RT-qPCR, ELISA, Western blot, and HE staining revealed that miR-34a inhibitor suppressed ECM degradation and inflammatory response of chondrocytes and cartilage tissues. By contrast, downregulation of DNMT3B and MCL1 reversed the repressive effects of miR-34a inhibitor in vitro and in vivo. Altogether, our findings establish that silencing of miR-34a by DNMT3B could effectively reduce chondrocyte ECM degradation and inflammatory response in mice by targeting MCL1 and mediating the downstream PI3K/AKT pathway. This present study revealed that miR-34a knockdown might develop a novel intervention for OA treatment.
format	article
author	Shouliang Xiong Yong Zhao Tiantong Xu
author_facet	Shouliang Xiong Yong Zhao Tiantong Xu
author_sort	Shouliang Xiong
title	DNA methyltransferase 3 beta mediates the methylation of the microRNA-34a promoter and enhances chondrocyte viability in osteoarthritis
title_short	DNA methyltransferase 3 beta mediates the methylation of the microRNA-34a promoter and enhances chondrocyte viability in osteoarthritis
title_full	DNA methyltransferase 3 beta mediates the methylation of the microRNA-34a promoter and enhances chondrocyte viability in osteoarthritis
title_fullStr	DNA methyltransferase 3 beta mediates the methylation of the microRNA-34a promoter and enhances chondrocyte viability in osteoarthritis
title_full_unstemmed	DNA methyltransferase 3 beta mediates the methylation of the microRNA-34a promoter and enhances chondrocyte viability in osteoarthritis
title_sort	dna methyltransferase 3 beta mediates the methylation of the microrna-34a promoter and enhances chondrocyte viability in osteoarthritis
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/eb8b0633d16c4208b9da4a29187208f0
work_keys_str_mv	AT shouliangxiong dnamethyltransferase3betamediatesthemethylationofthemicrorna34apromoterandenhanceschondrocyteviabilityinosteoarthritis AT yongzhao dnamethyltransferase3betamediatesthemethylationofthemicrorna34apromoterandenhanceschondrocyteviabilityinosteoarthritis AT tiantongxu dnamethyltransferase3betamediatesthemethylationofthemicrorna34apromoterandenhanceschondrocyteviabilityinosteoarthritis
_version_	1718405029971361792

DNA methyltransferase 3 beta mediates the methylation of the microRNA-34a promoter and enhances chondrocyte viability in osteoarthritis

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