N-methyladenosine (mA) methyltransferase METTL3-mediated LINC00680 accelerates osteoarthritis through mA/SIRT1 manner.

Increasing evidence suggest the biological roles of N-methyladenosine (mA) and long noncoding RNAs (lncRNAs) in the bone disease, especially osteoarthritis (OA). However, the interaction of mA and lncRNA in osteoarthritis is still unclear. Here, we found that a mA-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, mA methyltransferase METTL3 combined tithe the mA site of LINC00680 to up-regulate its expression. Moreover, LINC00680 interacted with SIRT1 mRNA through binding at mA site on SIRT1 mRNA 3'-UTR, thereby enhancing the stability of SIRT1 mRNA. Overall, these findings exhibited a role of LINC00680/mA/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.