Role of lncRNA XIST/miR-146a Axis in Matrix Degradation and Apoptosis of Osteoarthritic Chondrocytes Through Regulation of MMP-13 and BCL2.

IF 3.6 3区 生物学 Q1 BIOLOGY
Sara Cheleschi, Nicola Mondanelli, Iole Seccafico, Roberta Corsaro, Elena Moretti, Giulia Collodel, Antonella Fioravanti
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引用次数: 0

Abstract

Growing evidence demonstrates the critical roles of long non-coding RNAs (lncRNAs) in osteoarthritis (OA) pathogenesis. The lncRNA XIST is one of the most commonly studied; however, its function remains unclear. This study aimed to research the molecular mechanism of XIST in human OA chondrocytes. Cells were transfected with small interfering RNA against XIST or with a microRNA (miR)-146a inhibitor in the presence of interleukin (IL)-1β. Viability was detected using MTT; apoptosis using cytometry; and XIST, miR-146a, B-cell lymphoma (BCL)2, and metalloproteinase (MMP)-13 expression using real-time PCR. The analysis of p50 and p65 nuclear factor (NF)-κB was conducted using PCR and immunofluorescence. Our findings showed that XIST was highly expressed in OA chondrocytes when compared to T/C-28a2 lines. Furthermore, XIST silencing significantly promoted survival and limited apoptosis, with a concomitant over expression of BCL2, reduction in MMP-13 mRNA, and NF-κB activation after IL-1β stimulus. Conversely, miR-146a was significantly down-regulated in OA cells, while its levels were increased following XIST silencing; moreover, miR-146a inhibition induced opposite results to those caused by XIST. Finally, the down-regulation of XIST was correlated to the over-expression of miR-146a, with a consequent modulation of BCL2, MMP-13, and NF-κB. This study suggests an influence of the XIST/miR-146a axis on the viability, apoptosis, and matrix degradation occurring in OA.

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来源期刊
Biology-Basel
Biology-Basel Biological Science-Biological Science
CiteScore
5.70
自引率
4.80%
发文量
1618
审稿时长
11 weeks
期刊介绍: Biology (ISSN 2079-7737) is an international, peer-reviewed, quick-refereeing open access journal of Biological Science published by MDPI online. It publishes reviews, research papers and communications in all areas of biology and at the interface of related disciplines. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. Electronic files regarding the full details of the experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material.
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