The occurrence of osteoarthritis is closely related to chondrocyte dysfunction caused by cellular inflammatory response and matrix degradation, which seriously affect the quality of life of patients. Therefore, this study aimed to investigate the role of potassium voltage-gated channel subfamily Q member 1 overlapping transcript 1 (KCNQ1OT1), a member of the lncRNA voltage-gated channel subfamily Q, in the development of osteoarthritis. In this study, RT-qPCR results showed that KCNQ1OT1 expression was downregulated in osteoarthritic chondrocytes compared with normal chondrocytes. In addition, upregulation of KCNQ1OT1 significantly enhanced the viability of osteoarthritic chondrocytes, inhibited cell apoptosis, and reduced the release of inflammatory cytokines and metal matrix enzymes. Next, bioinformatics analysis and luciferase reporter gene analysis predicted and validated the targeting relationship between KCNQ1OT1 and miR-218-5p. We found that the expression of miR-218-5p was significantly upregulated in osteoarthritic chondrocytes, and knockdown of miR-218-5p significantly enhanced the viability of osteoarthritic chondrocytes, inhibited apoptosis, and decreased the abundance of inflammatory cytokines and metal matrix enzymes. Furthermore, the targeting relationship between miR-218-5p and recombinant phosphoinositide-3-kinase class-2-alpha polypeptide (PIK3C2A) was identified, and overexpression of PIK3C2A enhanced cell viability, and reduced apoptosis and secretion of inflammatory factors. Finally, we found that miR-218-5p overexpression reversed the protective effect of overexpression of KCNQ1OT1 or PIK3C2A on osteoarthritic chondrocytes. In conclusion, our results demonstrated that KCNQ1OT1 upregulated PIK3C2A and activated the PI3K/AKT/mTOR pathway to reduce chondrocyte dysfunction by targeting miR-218-5p, providing new insights into the pathogenesis of osteoarthritis.
[1]First Hosp Jilin Univ, Dept Orthpaed, 3302 Jilin Rd, Changchun 130000, Jilin, Peoples R China.
[2]First Hosp Jilin Univ, Dept Anesthesiol, Changchun 130000, Jilin, Peoples R China.
[3]Jilin Prov Tumor Hosp, Dept Radiotherapy 3, Changchun 130012, Jilin, Peoples R China.
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