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LncRNA MALAT1 promotes tenogenic differentiation of tendon-derived stem cells via regulating the miR-378a-3p/MAPK1 axis

Tendinopathy is a type of chronic injury caused by repeated pulling. Previous studies have reported that long non-coding RNA MALAT1 (MALAT1) regulates a variety of genes affecting bone metabolism. This study aimed to explore the role of the MALAT1 in tendon injury in vivo and in vitro. Human tendon-...

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Detalles Bibliográficos
Autores principales: Zhao, Zhe, Liu, Jianquan, Deng, Zhiqin, Chen, Xiaoqiang, Li, Wencui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9275883/
https://www.ncbi.nlm.nih.gov/pubmed/35635083
http://dx.doi.org/10.1080/21655979.2022.2076507
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author Zhao, Zhe
Liu, Jianquan
Deng, Zhiqin
Chen, Xiaoqiang
Li, Wencui
author_facet Zhao, Zhe
Liu, Jianquan
Deng, Zhiqin
Chen, Xiaoqiang
Li, Wencui
author_sort Zhao, Zhe
collection PubMed
description Tendinopathy is a type of chronic injury caused by repeated pulling. Previous studies have reported that long non-coding RNA MALAT1 (MALAT1) regulates a variety of genes affecting bone metabolism. This study aimed to explore the role of the MALAT1 in tendon injury in vivo and in vitro. Human tendon-derived stem cells (TDSCs) were treated with TGF β1. Eighteen Sprague-Dawley rats were used to establish the tendinopathy animal model. Sirius Red staining and colorimetric assays were conducted to analyze the collagen content. RT-qPCR was performed to measure the mRNA levels. Western blotting was performed to measure the MAPK1 protein levels. Additionally, hematoxylin and eosin (HE) and immunohistochemical staining were used to analyze the cell number and the content of collagen type 1 and Thbs, respectively. MALAT1 expression was upregulated in TGF β1 treated TDSCs, and MALAT1 knockdown downregulated Scleraxis, Mohawk homeobox, Collagen 1A1, Fibromodulin, Matrix metallopeptidase 3, and Thrombospondin 4 in TGF β1 treated TDSCs. Bioinformatics analysis showed that miR-378a-3p was the target of MALAT1 and MAPK1, and dual-luciferase reporter assay indicated that both MALAT1 and MAPK1 could bind to miR-378a-3p. Furthermore, miR-378a-3p knockdown reversed the effect of si-MALAT1, whereas overexpression of MAPK1 reversed the effect of the miR-378a-3p mimic. Finally, MALAT1 expression was downregulated in tendinopathy rats, and MALAT1 overexpression healed tendon injury in them. MALAT1 regulated the tenogenic differentiation of TDSCs by regulating the miR-378a-3p/MAPK1 axis. Our results therefore indicate that targeting the MALAT1/miR-378a-3p/MAPK1 axis may be a promising avenue for the treatment of tendinopathy.
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spelling pubmed-92758832022-07-13 LncRNA MALAT1 promotes tenogenic differentiation of tendon-derived stem cells via regulating the miR-378a-3p/MAPK1 axis Zhao, Zhe Liu, Jianquan Deng, Zhiqin Chen, Xiaoqiang Li, Wencui Bioengineered Research Paper Tendinopathy is a type of chronic injury caused by repeated pulling. Previous studies have reported that long non-coding RNA MALAT1 (MALAT1) regulates a variety of genes affecting bone metabolism. This study aimed to explore the role of the MALAT1 in tendon injury in vivo and in vitro. Human tendon-derived stem cells (TDSCs) were treated with TGF β1. Eighteen Sprague-Dawley rats were used to establish the tendinopathy animal model. Sirius Red staining and colorimetric assays were conducted to analyze the collagen content. RT-qPCR was performed to measure the mRNA levels. Western blotting was performed to measure the MAPK1 protein levels. Additionally, hematoxylin and eosin (HE) and immunohistochemical staining were used to analyze the cell number and the content of collagen type 1 and Thbs, respectively. MALAT1 expression was upregulated in TGF β1 treated TDSCs, and MALAT1 knockdown downregulated Scleraxis, Mohawk homeobox, Collagen 1A1, Fibromodulin, Matrix metallopeptidase 3, and Thrombospondin 4 in TGF β1 treated TDSCs. Bioinformatics analysis showed that miR-378a-3p was the target of MALAT1 and MAPK1, and dual-luciferase reporter assay indicated that both MALAT1 and MAPK1 could bind to miR-378a-3p. Furthermore, miR-378a-3p knockdown reversed the effect of si-MALAT1, whereas overexpression of MAPK1 reversed the effect of the miR-378a-3p mimic. Finally, MALAT1 expression was downregulated in tendinopathy rats, and MALAT1 overexpression healed tendon injury in them. MALAT1 regulated the tenogenic differentiation of TDSCs by regulating the miR-378a-3p/MAPK1 axis. Our results therefore indicate that targeting the MALAT1/miR-378a-3p/MAPK1 axis may be a promising avenue for the treatment of tendinopathy. Taylor & Francis 2022-05-29 /pmc/articles/PMC9275883/ /pubmed/35635083 http://dx.doi.org/10.1080/21655979.2022.2076507 Text en © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Zhao, Zhe
Liu, Jianquan
Deng, Zhiqin
Chen, Xiaoqiang
Li, Wencui
LncRNA MALAT1 promotes tenogenic differentiation of tendon-derived stem cells via regulating the miR-378a-3p/MAPK1 axis
title LncRNA MALAT1 promotes tenogenic differentiation of tendon-derived stem cells via regulating the miR-378a-3p/MAPK1 axis
title_full LncRNA MALAT1 promotes tenogenic differentiation of tendon-derived stem cells via regulating the miR-378a-3p/MAPK1 axis
title_fullStr LncRNA MALAT1 promotes tenogenic differentiation of tendon-derived stem cells via regulating the miR-378a-3p/MAPK1 axis
title_full_unstemmed LncRNA MALAT1 promotes tenogenic differentiation of tendon-derived stem cells via regulating the miR-378a-3p/MAPK1 axis
title_short LncRNA MALAT1 promotes tenogenic differentiation of tendon-derived stem cells via regulating the miR-378a-3p/MAPK1 axis
title_sort lncrna malat1 promotes tenogenic differentiation of tendon-derived stem cells via regulating the mir-378a-3p/mapk1 axis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9275883/
https://www.ncbi.nlm.nih.gov/pubmed/35635083
http://dx.doi.org/10.1080/21655979.2022.2076507
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