N(6)-methyladenosine (m(6)A) methyltransferase METTL3-mediated LINC00680 accelerates osteoarthritis through m(6)A/SIRT1 manner

Increasing evidence suggest the biological roles of N(6)-methyladenosine (m(6)A) and long noncoding RNAs (lncRNAs) in the bone disease, especially osteoarthritis (OA). However, the interaction of m(6)A and lncRNA in osteoarthritis is still unclear. Here, we found that a m(6)A-related lncRNA LINC00680 upregulated in the OA tissue and IL-1β-induced isolated primary chondrocytes. Functionally, in IL-1β-induced chondrocytes, silencing of LINC00680 recovered the proliferation and repressed the extracellular matrix (ECM) degradation. Mechanistically, m(6)A methyltransferase METTL3 combined tithe the m(6)A site of LINC00680 to up-regulate its expression. Moreover, LINC00680 interacted with SIRT1 mRNA through binding at m(6)A site on SIRT1 mRNA 3′-UTR, thereby enhancing the stability of SIRT1 mRNA. Overall, these findings exhibited a role of LINC00680/m(6)A/SIRT1 mRNA complex in chondrocytes. Taken together, the present study intends to uncover the mechanism by which METTL3-mediated LINC00680 accelerates OA progression, which may provide novel insight for OA.