METTL14-mediated methylation of SLC25A3 mitigates mitochondrial damage in osteoblasts, leading to the improvement of osteoporosis

Osteoporosis is linked to impaired function of osteoblasts, and decreased expression of METTL14 may result in abnormal differentiation of these bone-forming cells. However, the specific impact of METTL14 on osteoblast differentiation and its underlying mechanisms are not yet fully understood. This study discovered a positive correlation between METTL14 expression and bone formation in specimens from osteoporosis patients and ovariectomized (OVX) mice. Additionally, METTL14 targeting of SLC25A3 contributed to the restoration of mitochondrial ROS levels and mitochondrial membrane potential in osteoblasts and promoted osteoblast differentiation. Moreover, in vivo experiments showed that METTL14 enhanced bone formation, and therapeutic introduction of METTL14 countered the decrease in bone formation in OVX mice. Overall, these findings emphasize the crucial role of the METTL14/SLC25A3 signaling axis in osteoblast activity, suggesting that this axis could be a potential target for improving osteoporosis. •METTL14 is vital for preserving osteoblast mitochondria balance, helping prevent osteoporosis.•SLC25A3 is expressed at low levels in individuals with osteoporosis.•METTL14 alleviates mitochondrial damage and promotes osteoblast differentiation by mediating SLC25A3 methylation.