Upregulated ox40l Can Be Inhibited by miR-146a-5p in Condylar Chondrocytes Induced by IL-1β and TNF-α: A Possible Regulatory Mechanism in Osteoarthritis

Introduction: Osteoarthritis (OA) is a common musculoskeletal disease characterized by pain, stiffness, limited activity, occasional effusion, and local inflammation. MiR-146 is one of the noncoding RNA closely related to OA, but the role of miR-146 in OA remains controversial. The tumour necrosis factor receptor OX40 is activated by its cognate ligand OX40L (TNFSF4) and functions as a T-cell costimulatory molecule. The T-cell functions, including cytokine production, expansion, and survival, are enhanced by the OX40 costimulatory signals. Methods: We established an inflammatory model of condylar chondrocytes induced by IL-1β and TNF-α and detected the expression of miRNA by miRNA sequencing. Then, cell transfection was used to study the role of miR146a-5p in OA. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and database analysis were used to screen out potential target genes of miR-146a-5p. A dual luciferase activity assay tested whether ox40l is the target gene of miR-146a-5p. Results: MiR-146a-5p and OX40L was upregulated after induced by IL-1β and TNF-α, miR-146a-5p reduced the production of inflammatory factors but had no effect on chondrophenotypic factors, and ox40l was targeted by miR-146a-5p. Conclusion: OX40L and miR-146a-5p of condylar chondrocytes in the inflammatory environment (induced by IL-1β and TNF-α) were significantly increased, miR-146a-5p is a protective factor in the inflammatory response, which can reduce the production of inflammatory factors, and miR-146a-5p may regulate T-cell-mediated immunity through targeting of ox40l in OA.