MicroRNA-140-5p represses chondrocyte pyroptosis and relieves cartilage injury in osteoarthritis by inhibiting cathepsin B/Nod-like receptor protein 3

Osteoarthritis (OA) is a degenerative joint disease. Dysregulated microRNA (miRNA) expressions are implicated in OA progression. Consequently, the current study set out to investigate the mechanism of miR-140-5p in OA cartilage injury. Firstly, the murine and cell models of OA were established, and...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Lei Zhang, Jianjun Qiu, Jixiang Shi, Shaoyang Liu, Hanlin Zou
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	osteoarthritis cartilage injury pyroptosis mir-140-5p ctsb nlrp3 co-immunoprecipitation Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/c9b37fd04d9b46ceb54de2896ce75b0f
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c9b37fd04d9b46ceb54de2896ce75b0f
record_format	dspace
spelling	oai:doaj.org-article:c9b37fd04d9b46ceb54de2896ce75b0f2021-12-01T14:41:00ZMicroRNA-140-5p represses chondrocyte pyroptosis and relieves cartilage injury in osteoarthritis by inhibiting cathepsin B/Nod-like receptor protein 32165-59792165-598710.1080/21655979.2021.1985342https://doaj.org/article/c9b37fd04d9b46ceb54de2896ce75b0f2021-12-01T00:00:00Zhttp://dx.doi.org/10.1080/21655979.2021.1985342https://doaj.org/toc/2165-5979https://doaj.org/toc/2165-5987Osteoarthritis (OA) is a degenerative joint disease. Dysregulated microRNA (miRNA) expressions are implicated in OA progression. Consequently, the current study set out to investigate the mechanism of miR-140-5p in OA cartilage injury. Firstly, the murine and cell models of OA were established, and cartilage tissues of OA mice were observed using hematoxylin and eosin staining and safranin O staining. Chondrocyte pyroptosis was further assessed using immunohistochemical and Calcein-AM/PI staining. The levels of gasdermin-D (GSDMD)-N, cleaved caspase-1, interleukin (IL)-1β, and IL-18 in cartilage tissues and cells were determined using Western blot and enzyme-linked immunosorbent assay kits. The targeting relationship between miR-140-5p and cathepsin B (CTSB) was verified using a dual-luciferase assay. Moreover, the binding of CTSB and Nod-like receptor protein 3 (NLRP3) was detected using co-immunoprecipitation assay. Lastly, the effects of NLRP3 activation and CTSB overexpression on chondrocyte pyroptosis were documented. It was found that OA induction aggravated cartilage tissue injury and enhanced chondrocyte pyroptosis. miR-140-5p was poorly-expressed in OA models, and miR-140-5p over-expression alleviated chondrocyte pyroptosis, as evidenced by decreased GSDMD-N, cleaved caspase-1, IL-1β, and IL-18 levels. miR-140-5p targeted the CTSB gene, whereas CTSB further bound to NLRP3 and activated the NLRP3 inflammasome. Additionally, CTSB over-expression or NLRP3 activation reversed the inhibitory effect of miR-140-5p on chondrocyte pyroptosis. Collectively, our findings revealed that miR-140-5p repressed chondrocyte pyroptosis and alleviated OA cartilage injury via inhibition of the CTSB/NLRP3. This study may confer a theoretical basis for the treatment of OA cartilage injury.Lei ZhangJianjun QiuJixiang ShiShaoyang LiuHanlin ZouTaylor & Francis Grouparticleosteoarthritiscartilage injurypyroptosismir-140-5pctsbnlrp3co-immunoprecipitationBiotechnologyTP248.13-248.65ENBioengineered, Vol 12, Iss 2, Pp 9949-9964 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	osteoarthritis cartilage injury pyroptosis mir-140-5p ctsb nlrp3 co-immunoprecipitation Biotechnology TP248.13-248.65
spellingShingle	osteoarthritis cartilage injury pyroptosis mir-140-5p ctsb nlrp3 co-immunoprecipitation Biotechnology TP248.13-248.65 Lei Zhang Jianjun Qiu Jixiang Shi Shaoyang Liu Hanlin Zou MicroRNA-140-5p represses chondrocyte pyroptosis and relieves cartilage injury in osteoarthritis by inhibiting cathepsin B/Nod-like receptor protein 3
description	Osteoarthritis (OA) is a degenerative joint disease. Dysregulated microRNA (miRNA) expressions are implicated in OA progression. Consequently, the current study set out to investigate the mechanism of miR-140-5p in OA cartilage injury. Firstly, the murine and cell models of OA were established, and cartilage tissues of OA mice were observed using hematoxylin and eosin staining and safranin O staining. Chondrocyte pyroptosis was further assessed using immunohistochemical and Calcein-AM/PI staining. The levels of gasdermin-D (GSDMD)-N, cleaved caspase-1, interleukin (IL)-1β, and IL-18 in cartilage tissues and cells were determined using Western blot and enzyme-linked immunosorbent assay kits. The targeting relationship between miR-140-5p and cathepsin B (CTSB) was verified using a dual-luciferase assay. Moreover, the binding of CTSB and Nod-like receptor protein 3 (NLRP3) was detected using co-immunoprecipitation assay. Lastly, the effects of NLRP3 activation and CTSB overexpression on chondrocyte pyroptosis were documented. It was found that OA induction aggravated cartilage tissue injury and enhanced chondrocyte pyroptosis. miR-140-5p was poorly-expressed in OA models, and miR-140-5p over-expression alleviated chondrocyte pyroptosis, as evidenced by decreased GSDMD-N, cleaved caspase-1, IL-1β, and IL-18 levels. miR-140-5p targeted the CTSB gene, whereas CTSB further bound to NLRP3 and activated the NLRP3 inflammasome. Additionally, CTSB over-expression or NLRP3 activation reversed the inhibitory effect of miR-140-5p on chondrocyte pyroptosis. Collectively, our findings revealed that miR-140-5p repressed chondrocyte pyroptosis and alleviated OA cartilage injury via inhibition of the CTSB/NLRP3. This study may confer a theoretical basis for the treatment of OA cartilage injury.
format	article
author	Lei Zhang Jianjun Qiu Jixiang Shi Shaoyang Liu Hanlin Zou
author_facet	Lei Zhang Jianjun Qiu Jixiang Shi Shaoyang Liu Hanlin Zou
author_sort	Lei Zhang
title	MicroRNA-140-5p represses chondrocyte pyroptosis and relieves cartilage injury in osteoarthritis by inhibiting cathepsin B/Nod-like receptor protein 3
title_short	MicroRNA-140-5p represses chondrocyte pyroptosis and relieves cartilage injury in osteoarthritis by inhibiting cathepsin B/Nod-like receptor protein 3
title_full	MicroRNA-140-5p represses chondrocyte pyroptosis and relieves cartilage injury in osteoarthritis by inhibiting cathepsin B/Nod-like receptor protein 3
title_fullStr	MicroRNA-140-5p represses chondrocyte pyroptosis and relieves cartilage injury in osteoarthritis by inhibiting cathepsin B/Nod-like receptor protein 3
title_full_unstemmed	MicroRNA-140-5p represses chondrocyte pyroptosis and relieves cartilage injury in osteoarthritis by inhibiting cathepsin B/Nod-like receptor protein 3
title_sort	microrna-140-5p represses chondrocyte pyroptosis and relieves cartilage injury in osteoarthritis by inhibiting cathepsin b/nod-like receptor protein 3
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/c9b37fd04d9b46ceb54de2896ce75b0f
work_keys_str_mv	AT leizhang microrna1405prepresseschondrocytepyroptosisandrelievescartilageinjuryinosteoarthritisbyinhibitingcathepsinbnodlikereceptorprotein3 AT jianjunqiu microrna1405prepresseschondrocytepyroptosisandrelievescartilageinjuryinosteoarthritisbyinhibitingcathepsinbnodlikereceptorprotein3 AT jixiangshi microrna1405prepresseschondrocytepyroptosisandrelievescartilageinjuryinosteoarthritisbyinhibitingcathepsinbnodlikereceptorprotein3 AT shaoyangliu microrna1405prepresseschondrocytepyroptosisandrelievescartilageinjuryinosteoarthritisbyinhibitingcathepsinbnodlikereceptorprotein3 AT hanlinzou microrna1405prepresseschondrocytepyroptosisandrelievescartilageinjuryinosteoarthritisbyinhibitingcathepsinbnodlikereceptorprotein3
_version_	1718405021131866112

MicroRNA-140-5p represses chondrocyte pyroptosis and relieves cartilage injury in osteoarthritis by inhibiting cathepsin B/Nod-like receptor protein 3

Ejemplares similares