LINC02288 promotes chondrocyte apoptosis and inflammation through miR‐374a‐3p targeting RTN3

Background Dysregulation of long non‐coding RNAs (lncRNAs) is related to the occurrence of osteoarthritis (OA). In the present study, we explored the role of LINC02288 and its regulatory mechanism in OA development. Methods GSE113825 was obtained from Gene Expression Omnibus (GEO) database and analyzed to identify the differentially expressed lncRNAs in OA. Gene enrichment analyses and Kyoto Encyclopedia of Genes and Genomes biological process analysis were performed through Metascape (http://metascape.org/gp). The interactions among LINC02288, miR‐374a‐3p and RTN3 were determined using RNA immunoprecipitation (RIP) assays and dual luciferase reporter assays. Chondrocyte apoptosis was examined using flow cytometry. Western blot assays were conducted to assess the pro‐apoptotic and anti‐apoptotic markers. Results We identified a total of 4,491 differentially expressed lncRNAs. We focused on LINC02288 as the top‐ranked up‐regulated lncRNA in OA as indicated by a significant p‐value. LINC02288 was significantly up‐regulated, which was further verified by a real‐time polymerase chain reaction. Down‐regulation of LINC02288 significantly reduced the apoptosis of OA chondrocytes induced by interleukin‐1β and the production of pro‐inflammatory cytokines. These effects were further verified in an OA rat model. An RIP assay and dual luciferase assay further confirmed that LINC02288 served as a sponge of miR‐374a‐3p. Moreover, the overexpression of RTN3 could partially reverse the effects of LINC02288 knockdown, mediating inhibitory effects on chondrocyte apoptosis and the inflammatory response. Down‐regulation of LINC02288 alleviated OA development in an in vivo OA animal model. Conclusions Our findings indicate that LINC02288 contributes to OA progression by targeting the miR‐374a‐3p/RTN3 axis, which might provide a promising molecular therapy strategy for OA. LINC02288 targets RTN3 to regulate chondrocytes apoptosis via acting as miR‐374a‐3p sponge in osteoarthritis.