A long non-coding RNA, HOTAIR, promotes cartilage degradation in osteoarthritis by inhibiting WIF-1 expression and activating Wnt pathway.

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

A long non-coding RNA, HOTAIR, promotes cartilage degradation in osteoarthritis by inhibiting WIF-1 expression and activating Wnt pathway.

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

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Publisher:: BMC
Publication Type:: Journal Article
Citation:: BMC molecular and cell biology, 2020, 21, (1), pp. 53
Issue Date:: 2020-07-10

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Field	Value	Language
dc.contributor.author	Yang, Y
dc.contributor.author	Xing, D
dc.contributor.author	Wang, Y
dc.contributor.author	Jia, H
dc.contributor.author	Li, B
dc.contributor.author	Li, JJ
dc.date.accessioned	2020-10-17T01:10:08Z
dc.date.available	2020-07-02
dc.date.available	2020-10-17T01:10:08Z
dc.date.issued	2020-07-10
dc.identifier.citation	BMC molecular and cell biology, 2020, 21, (1), pp. 53
dc.identifier.issn	2661-8850
dc.identifier.issn	2661-8850
dc.identifier.uri	http://hdl.handle.net/10453/143325
dc.description.abstract	BACKGROUND:Long noncoding RNAs (lncRNAs) are recently found to be critical regulators of the epigenome. However, our knowledge of their role in osteoarthritis (OA) development is limited. This study investigates the mechanism by which HOTAIR, a key lncRNA with elevated expression in OA, affects OA disease progression. RESULTS:HOTAIR expression was greatly elevated in osteoarthritic compared to normal chondrocytes. Silencing and over-expression of HOTAIR in SW1353 cells respectively reduced and increased the expression of genes associated with cartilage degradation in OA. Investigation of molecular pathways revealed that HOTAIR acted directly on Wnt inhibitory factor 1 (WIF-1) by increasing histone H3K27 trimethylation in the WIF-1 promoter, leading to WIF-1 repression that favours activation of the Wnt/β-catenin pathway. CONCLUSIONS:Activation of Wnt/β-catenin signalling by HOTAIR through WIF-1 repression in osteoarthritic chondrocytes increases catabolic gene expression and promotes cartilage degradation. This is the first study to demonstrate a direct link between HOTAIR, WIF-1 and OA progression, which may be useful for future investigations into disease biomarkers or therapeutic targets.
dc.format	Electronic
dc.language	eng
dc.publisher	BMC
dc.relation	http://purl.org/au-research/grants/nhmrc/1120249
dc.relation.ispartof	BMC molecular and cell biology
dc.relation.isbasedon	10.1186/s12860-020-00299-6
dc.rights	info:eu-repo/semantics/openAccess
dc.title	A long non-coding RNA, HOTAIR, promotes cartilage degradation in osteoarthritis by inhibiting WIF-1 expression and activating Wnt pathway.
dc.type	Journal Article
utslib.citation.volume	21
utslib.location.activity	England
utslib.for	0903 Biomedical Engineering
utslib.for	1103 Clinical Sciences
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
pubs.organisational-group	/University of Technology Sydney
utslib.copyright.status	open_access	*
dc.date.updated	2020-10-17T01:09:38Z
pubs.issue	1
pubs.publication-status	Published
pubs.volume	21
utslib.citation.issue	1

Abstract:

BACKGROUND:Long noncoding RNAs (lncRNAs) are recently found to be critical regulators of the epigenome. However, our knowledge of their role in osteoarthritis (OA) development is limited. This study investigates the mechanism by which HOTAIR, a key lncRNA with elevated expression in OA, affects OA disease progression. RESULTS:HOTAIR expression was greatly elevated in osteoarthritic compared to normal chondrocytes. Silencing and over-expression of HOTAIR in SW1353 cells respectively reduced and increased the expression of genes associated with cartilage degradation in OA. Investigation of molecular pathways revealed that HOTAIR acted directly on Wnt inhibitory factor 1 (WIF-1) by increasing histone H3K27 trimethylation in the WIF-1 promoter, leading to WIF-1 repression that favours activation of the Wnt/β-catenin pathway. CONCLUSIONS:Activation of Wnt/β-catenin signalling by HOTAIR through WIF-1 repression in osteoarthritic chondrocytes increases catabolic gene expression and promotes cartilage degradation. This is the first study to demonstrate a direct link between HOTAIR, WIF-1 and OA progression, which may be useful for future investigations into disease biomarkers or therapeutic targets.

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http://hdl.handle.net/10453/143325