Methylase METTL3 regulates oxidative stress-induced osteoblast apoptosis through Wnt/β-catenin signaling pathway.

The latest research shows that the imbalance of reactive oxygen species (ROS) leads to oxidative stress-induced osteoblast apoptosis, which is an important factor in the development of osteoporosis. Methyltransferase like 3 (METTL3) is the most widely known methyltransferase, which has a marked effect on the cells of oxidative stress reaction. However, the precise mechanism through which METTL3 mediates oxidative stress-induced osteoblast apoptosis remains uncleared. An ovariectomized (OVX) rat model was established and histochemical staining were used to evaluate bone mass and the expression of METTL3. The oxidative stress state of bone tissue and the expression of METTL3 were detected by RT-PCR. The reactive oxygen species (ROS) levels were detected by DCFH-DA staining. Cell death and apoptosis were detected by CCK8, Hoechst PI double dyeing and TUNEL staining. The mitochondrial membrane potential was detected by JC-1 fluorescent staining. The expression of N6-methyladenosine, the protein levels of cell apoptosis and Wnt/β-catenin signal were detected by RT-PCR and western blot. We demonstrated that METTL3 was highly expressed in OVX-induced osteoporosis, and it inhibited oxidative stress-induced apoptosis of MC3T3-E1 cells by downregulating the ROS-mediated activation of the Wnt/β-catenin signaling pathway in osteoblasts. In addition, under oxidative stress, ROS accumulation further inhibited METTL3 expression and activated the Wnt/β-catenin signaling pathway, which ultimately led to apoptosis of MC3T3-E1 cells. This study investigated the important role of METTL3 in oxidative stress-induced osteoblast apoptosis. It may be a new therapeutic target for osteoporosis from the perspective of oxidative stress.