LINC00312 affects the progression of osteoarthritis by targeting miR-331-3p/DUSP5 axis.

As a chronic degenerative disease, osteoarthritis (OA) manifests through articular cartilage breakdown and ongoing inflammatory processes in joints. Recently, long non-coding RNAs (lncRNAs) have been participated in pathological process of OA through epigenetic regulation and molecular signaling axis. This study aimed to verify whether LINC00312 regulates DUSP5 expression by adsorbing miR-331-3p as a competitive endogenous RNA (ceRNA) in OA, thereby exerting a cartilage-protective effect. Expressions of LINC00312, miR-331-3p, and dual-specific protein phosphatase 5 (DUSP5) in patient tissues and chondrocytes were detected by reverse transcription-quantitative PCR (RT-qPCR). An in vitro OA model was constructed by stimulating chondrocytes with IL-1β. Cell viability and apoptosis were assessed via cell counting kit-8 (CCK-8) assays and flow cytometry. The levels of chondrogenic-related genes and proinflammatory factors were detected by RT-qPCR and enzyme-linked immunosorbent assay (ELISA). Interaction of miR-331-3p with LINC00312 and DUSP5 was detected via dual luciferase assays and RIP assays. Correlation between LINC00312, miR-331-3p, and DUSP5 in patients with OA was analyzed using Pearson correlation analysis. In OA patients' cartilage tissue and IL-1β-induced OA models, LINC00312 and DUSP5 expression decreased while miR-331- 3p expression increased. Overexpression of LINC00312 ameliorated cell injury induced by IL-1β stimulation, enhanced cell viability, and reduced apoptosis, MMP13, ADAMTS5, IL-6, and IL-8 levels. miR-331-3p negatively correlated with LINC00312, and upregulation of miR-331-3p reversed the protective effect of LINC00312. Additionally, DUSP5 was a direct target of miR-331-3p, and LINC00312 and miR-331-3p jointly regulated DUSP5 expression. LINC00312 alleviates IL-1β-induced chondrocyte inflammation and apoptosis by acting as a ceRNA to regulate the miR-331-3p/DUSP5 axis. This suggests that LINC00312 may serve as a novel therapeutic target for OA.