MicroRNA-1 Modulates Chondrocyte Phenotype by Regulating FZD7 of Wnt/β-Catenin Signaling Pathway.

Yang, Y; Wang, Y; Jia, H; Li, B; Xing, D; Li, JJ

MicroRNA-1 Modulates Chondrocyte Phenotype by Regulating FZD7 of Wnt/β-Catenin Signaling Pathway.

Yang, Y Wang, Y Jia, H Li, B Xing, D Li, JJ

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Publisher:: SAGE Publications
Publication Type:: Journal Article
Citation:: Cartilage, 2021, pp. 1947603520973255
Issue Date:: 2021

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Field	Value	Language
dc.contributor.author	Yang, Y
dc.contributor.author	Wang, Y
dc.contributor.author	Jia, H
dc.contributor.author	Li, B
dc.contributor.author	Xing, D
dc.contributor.author	Li, JJ
dc.date.accessioned	2021-07-30T09:42:25Z
dc.date.available	2021-07-30T09:42:25Z
dc.date.issued	2021
dc.identifier.citation	Cartilage, 2021, pp. 1947603520973255
dc.identifier.issn	1947-6035
dc.identifier.issn	1947-6043
dc.identifier.uri	http://hdl.handle.net/10453/150011
dc.description.abstract	<h4>Objective</h4>Osteoarthritis (OA) is an incurable joint disease characterized by pronounced pain. MicroRNAs constitute epigenetic mechanisms that may affect OA progression by contributing to changes in chondrocyte phenotype. This study investigates for the first time whether there is a link between miRNA-1 (miR-1) and OA pathogenesis, and the molecular mechanisms involved.<h4>Design</h4>OA-associated gene expression, including MMP-13, ADAMTS5, and COL2A1 was compared in chondrocytes from non-OA and OA cartilage, and in SW1353 cells over- and underexpressing miR-1. Bioinformatics and luciferase reporter assay were conducted to confirm whether FZD7 was a target of miR-1. The effects of miR-1 on FZD7 expression and downstream Wnt/β-catenin signalling were investigated.<h4>Results</h4>Non-OA and OA chondrocytes differed significantly in the expression of miR-1 and OA-associated genes. MiR-1 over- and underexpression in SW1353 cells, respectively, reduced and enhanced gene expression associated with cartilage catabolism. FZD7, which has an important role in the Wnt/β-catenin signaling pathway, was shown to be a potential target of miR-1. MiR-1 binding to FZD7 increased the levels of phosphorylated (inactivated) β-catenin, thereby preventing downstream β-catenin signaling.<h4>Conclusions</h4>Inhibition of Wnt/β-catenin signaling by miR-1 in chondrocytes may attenuate the expression of genes that regulate the activity of catabolic enzymes. This finding may be useful for future investigations of molecular targets for OA treatment.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	SAGE Publications
dc.relation	http://purl.org/au-research/grants/nhmrc/1120249
dc.relation.ispartof	Cartilage
dc.relation.isbasedon	10.1177/1947603520973255
dc.rights	info:eu-repo/semantics/openAccess
dc.rights	Yang, Yang; Wang, Yawei; Jia, Haobo; Li, Bing; Xing, Dan; Li, Jiao Jiao \| MicroRNA-1 Modulates Chondrocyte Phenotype by Regulating FZD7 of Wnt/β-Catenin Signaling Pathway. \| \| Cartilage , 2021, pp. 1947603520973255-1947603520973255 (Copyright © [2021]. DOI: 10.1177/1947603520973255
dc.rights	Yang, Yang; Wang, Yawei; Jia, Haobo; Li, Bing; Xing, Dan; Li, Jiao Jiao \| MicroRNA-1 Modulates Chondrocyte Phenotype by Regulating FZD7 of Wnt/β-Catenin Signaling Pathway. \| Cartilage \| [10.1177/1329878X20932356
dc.subject	0903 Biomedical Engineering, 1004 Medical Biotechnology, 1103 Clinical Sciences
dc.title	MicroRNA-1 Modulates Chondrocyte Phenotype by Regulating FZD7 of Wnt/β-Catenin Signaling Pathway.
dc.type	Journal Article
utslib.location.activity	United States
utslib.for	0903 Biomedical Engineering
utslib.for	1004 Medical Biotechnology
utslib.for	1103 Clinical Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
utslib.copyright.status	open_access	*
pubs.consider-herdc	false
dc.date.updated	2021-07-30T09:42:22Z
pubs.publication-status	Published

Abstract:

Objective

Osteoarthritis (OA) is an incurable joint disease characterized by pronounced pain. MicroRNAs constitute epigenetic mechanisms that may affect OA progression by contributing to changes in chondrocyte phenotype. This study investigates for the first time whether there is a link between miRNA-1 (miR-1) and OA pathogenesis, and the molecular mechanisms involved.

Design

OA-associated gene expression, including MMP-13, ADAMTS5, and COL2A1 was compared in chondrocytes from non-OA and OA cartilage, and in SW1353 cells over- and underexpressing miR-1. Bioinformatics and luciferase reporter assay were conducted to confirm whether FZD7 was a target of miR-1. The effects of miR-1 on FZD7 expression and downstream Wnt/β-catenin signalling were investigated.

Results

Non-OA and OA chondrocytes differed significantly in the expression of miR-1 and OA-associated genes. MiR-1 over- and underexpression in SW1353 cells, respectively, reduced and enhanced gene expression associated with cartilage catabolism. FZD7, which has an important role in the Wnt/β-catenin signaling pathway, was shown to be a potential target of miR-1. MiR-1 binding to FZD7 increased the levels of phosphorylated (inactivated) β-catenin, thereby preventing downstream β-catenin signaling.

Conclusions

Inhibition of Wnt/β-catenin signaling by miR-1 in chondrocytes may attenuate the expression of genes that regulate the activity of catabolic enzymes. This finding may be useful for future investigations of molecular targets for OA treatment.

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http://hdl.handle.net/10453/150011