METTL3 inhibits LINC00312 to suppress osteoporosis progression in a YTHDF2‑dependent manner.

The regulation of methylation and non‑coding RNAs plays important roles in the pathogenesis of osteoporosis. Most microRNAs (miRNAs or miRs) exert their biological functions through target genes. Long non‑coding RNAs function as competing endogenous RNAs. hFOB 1.19 cells were transfected with miR‑4765, LINC00312 and METTL3‑related molecules. LINC00312 and miR‑4765 expression was detected by PCR, whereas cleaved caspase 3 and FOXK2/SFRP1 levels were detected by western blotting. Micro‑computed tomography was used to detect the bone microstructure. Diabetic mice received treatments targeting METTL3 and LINC00312. FOXK2/SFRP1 expression was detected using PCR and immunohistochemistry. The results showed that miR‑4765 overexpression reduced FOXK2/SFRP1 and cleaved caspase 3 expression, causing cell apoptosis. LINC00312 inhibition was observed both in vitro and in vivo. LINC00312 binds directly to miR‑4765, whereas miR‑4765 binds directly to FOXK2/SFRP1. METTL3 and YTHDF2 directly bind LINC00312 and reduce its expression by altering its methylation levels. In conclusion, LINC00312 promotes the apoptosis of hFOB 1.19 cells by targeting the miR‑4765/FOXK2/SFRP1 axis, and METTL3 regulates LINC00312 expression in a YTHDF2‑dependent manner.