Cargando…

LINC00473 exacerbates osteoarthritis development by promoting chondrocyte apoptosis and proinflammatory cytokine production through the miR-424-5p/LY6E axis

Osteoarthritis (OA) is a common degenerative joint disease that has been identified as one of the major health burdens in aging individuals. Long non-coding RNAs (lncRNAs) participate in the development of diverse diseases, including OA. Among them, lncRNA long intergenic non-protein coding RNA 473...

Descripción completa

Detalles Bibliográficos
Autores principales: Fan, Guiyong, Liu, Jinlian, Zhang, Yesong, Guan, Xinxian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438674/
https://www.ncbi.nlm.nih.gov/pubmed/34539843
http://dx.doi.org/10.3892/etm.2021.10682
_version_ 1783752393573269504
author Fan, Guiyong
Liu, Jinlian
Zhang, Yesong
Guan, Xinxian
author_facet Fan, Guiyong
Liu, Jinlian
Zhang, Yesong
Guan, Xinxian
author_sort Fan, Guiyong
collection PubMed
description Osteoarthritis (OA) is a common degenerative joint disease that has been identified as one of the major health burdens in aging individuals. Long non-coding RNAs (lncRNAs) participate in the development of diverse diseases, including OA. Among them, lncRNA long intergenic non-protein coding RNA 473 (LINC00473) is one of the few upregulated lncRNAs. The present study aimed to explore the role of LINC00473 and its regulatory mechanism in OA development. Flow cytometry analyses and ELISA were carried out to detect chondrocyte apoptosis and the concentration of proinflammatory cytokines, respectively. The results suggested that LINC00473 knockdown significantly reduced chondrocyte apoptosis and the production of proinflammatory cytokines in IL-1β-stimulated C28/I2 cells compared with transfection with small interfering RNA-negative control (si-NC). Western blot analyses were performed to examine protein levels of apoptotic markers (caspase-3, Bax and Bcl-2) in C28/I2 cells. Subsequently, an OA rat model was established to explore the role of LINC00473 in vivo. The results indicated that, compared with the OA + adeno-associated virus si-NC group, LINC00473 knockdown significantly suppressed the degradation of chondrocyte extracellular matrix and the production of proinflammatory cytokines in OA model rats. Furthermore, bioinformatics analysis, luciferase reporter and RNA immunoprecipitation assays indicated that LINC00473 served as a microRNA (miR)-424-5p sponge in C28/I2 cells, and that lymphocyte antigen 6 locus E (LY6E) was the downstream target. In addition, the inhibitory effects of LINC00473 knockdown on chondrocyte apoptosis and the inflammatory response could be reversed by LY6E overexpression in IL-1β-stimulated C28/I2 cells. In summary, the findings indicated that LINC00473 contributed to OA progression by modulating the miR-424-5p/LY6E axis, which may serve as a potential therapeutic strategy for patients with OA.
format Online
Article
Text
id pubmed-8438674
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher D.A. Spandidos
record_format MEDLINE/PubMed
spelling pubmed-84386742021-09-17 LINC00473 exacerbates osteoarthritis development by promoting chondrocyte apoptosis and proinflammatory cytokine production through the miR-424-5p/LY6E axis Fan, Guiyong Liu, Jinlian Zhang, Yesong Guan, Xinxian Exp Ther Med Articles Osteoarthritis (OA) is a common degenerative joint disease that has been identified as one of the major health burdens in aging individuals. Long non-coding RNAs (lncRNAs) participate in the development of diverse diseases, including OA. Among them, lncRNA long intergenic non-protein coding RNA 473 (LINC00473) is one of the few upregulated lncRNAs. The present study aimed to explore the role of LINC00473 and its regulatory mechanism in OA development. Flow cytometry analyses and ELISA were carried out to detect chondrocyte apoptosis and the concentration of proinflammatory cytokines, respectively. The results suggested that LINC00473 knockdown significantly reduced chondrocyte apoptosis and the production of proinflammatory cytokines in IL-1β-stimulated C28/I2 cells compared with transfection with small interfering RNA-negative control (si-NC). Western blot analyses were performed to examine protein levels of apoptotic markers (caspase-3, Bax and Bcl-2) in C28/I2 cells. Subsequently, an OA rat model was established to explore the role of LINC00473 in vivo. The results indicated that, compared with the OA + adeno-associated virus si-NC group, LINC00473 knockdown significantly suppressed the degradation of chondrocyte extracellular matrix and the production of proinflammatory cytokines in OA model rats. Furthermore, bioinformatics analysis, luciferase reporter and RNA immunoprecipitation assays indicated that LINC00473 served as a microRNA (miR)-424-5p sponge in C28/I2 cells, and that lymphocyte antigen 6 locus E (LY6E) was the downstream target. In addition, the inhibitory effects of LINC00473 knockdown on chondrocyte apoptosis and the inflammatory response could be reversed by LY6E overexpression in IL-1β-stimulated C28/I2 cells. In summary, the findings indicated that LINC00473 contributed to OA progression by modulating the miR-424-5p/LY6E axis, which may serve as a potential therapeutic strategy for patients with OA. D.A. Spandidos 2021-11 2021-09-02 /pmc/articles/PMC8438674/ /pubmed/34539843 http://dx.doi.org/10.3892/etm.2021.10682 Text en Copyright: © Fan et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Fan, Guiyong
Liu, Jinlian
Zhang, Yesong
Guan, Xinxian
LINC00473 exacerbates osteoarthritis development by promoting chondrocyte apoptosis and proinflammatory cytokine production through the miR-424-5p/LY6E axis
title LINC00473 exacerbates osteoarthritis development by promoting chondrocyte apoptosis and proinflammatory cytokine production through the miR-424-5p/LY6E axis
title_full LINC00473 exacerbates osteoarthritis development by promoting chondrocyte apoptosis and proinflammatory cytokine production through the miR-424-5p/LY6E axis
title_fullStr LINC00473 exacerbates osteoarthritis development by promoting chondrocyte apoptosis and proinflammatory cytokine production through the miR-424-5p/LY6E axis
title_full_unstemmed LINC00473 exacerbates osteoarthritis development by promoting chondrocyte apoptosis and proinflammatory cytokine production through the miR-424-5p/LY6E axis
title_short LINC00473 exacerbates osteoarthritis development by promoting chondrocyte apoptosis and proinflammatory cytokine production through the miR-424-5p/LY6E axis
title_sort linc00473 exacerbates osteoarthritis development by promoting chondrocyte apoptosis and proinflammatory cytokine production through the mir-424-5p/ly6e axis
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438674/
https://www.ncbi.nlm.nih.gov/pubmed/34539843
http://dx.doi.org/10.3892/etm.2021.10682
work_keys_str_mv AT fanguiyong linc00473exacerbatesosteoarthritisdevelopmentbypromotingchondrocyteapoptosisandproinflammatorycytokineproductionthroughthemir4245ply6eaxis
AT liujinlian linc00473exacerbatesosteoarthritisdevelopmentbypromotingchondrocyteapoptosisandproinflammatorycytokineproductionthroughthemir4245ply6eaxis
AT zhangyesong linc00473exacerbatesosteoarthritisdevelopmentbypromotingchondrocyteapoptosisandproinflammatorycytokineproductionthroughthemir4245ply6eaxis
AT guanxinxian linc00473exacerbatesosteoarthritisdevelopmentbypromotingchondrocyteapoptosisandproinflammatorycytokineproductionthroughthemir4245ply6eaxis