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

doi:10.3892/etm.2021.10682

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

Authors:
- Guiyong Fan
- Jinlian Liu
- Yesong Zhang
- Xinxian Guan
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Affiliations: Department of Orthopedics, Suzhou Kowloon Hospital, Shanghai Jiangtong University School of Medicine, Suzhou, Jiangsu 215028, P.R. China, Department of Neonatology, Children's Hospital of Soochow University, Suzhou, Jiangsu 215025, P.R. China
Published online on: September 2, 2021 https://doi.org/10.3892/etm.2021.10682
Article Number: 1247
Copyright: © Fan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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