NEAT1/miR-181c Regulates Osteopontin (OPN)-Mediated Synoviocyte Proliferation in Osteoarthritis.

Osteoarthritis (OA) is characterized by progressive destruction of articular cartilage, resulting in significant disability. Inflammatory cytokines commonly initiate the extreme changes in the synovium and cartilage microenvironment of the OA patients, subsequently resulting in cell dysfunctions, especially synoviocyte dysfunction. We revealed that the expression of osteopontin (OPN), which has been reported to regulate expression of various inflammatory factors associating with the pathogenesis of OA including matrix metalloprotease 13 (MMP13), interlukine-6 and 8 (IL-6 and IL-8), is significantly upregulated in OA tissues. In the present study, online tools were used to screen out the candidate miRNAs of OPN. Among the candidate miRNAs, miR-181c inhibited OPN mRNA expression the most strongly. Ectopic expression of miR-181c significantly repressed synoviocyte proliferation, as well as the levels of OPN, MMP13, IL-6, and IL-8. Further, the candidate lncRNAs of miR-181c were screened out by using DianaTools; among which NEAT1 showed to inversely regulate miR-181c. By performing Luciferase assays, we revealed that NEAT1 competed with OPN for miR-181c binding. After NEAT1 knockdown, MMP13, IL-6, and IL-8 expression was reduced; the synoviocyte proliferation was repressed, as well as OPN protein levels; the suppressive effect of NETA1 knockdown on synoviocyte proliferation and the indicated factors were partially reversed by miR-181c inhibition. In OA tissues, OPN mRNA, and NEAT1 expression was upregulated, whereas miR-181c expression was downregulated, indicating that targeting NEAT1 to rescue miR-181c expression so as to inhibit OPN expression and synoviocyte proliferation might be an efficient strategy for OA treatment. J. Cell. Biochem. 118: 3775-3784, 2017.