MiR-103-3p targets the m6A methyltransferase METTL14 to inhibit osteoblastic bone formation

Impaired osteoblast function is involved in osteoporosis, and microRNA (miRNA) dysregulation may cause abnormal osteoblast osteogenic activity. However, the influence of miRNA on osteoblast activity and the underlying mechanisms remain elusive. In this study, miR-103-3p was found to be negatively correlated with bone formation in bone specimens from elderly women with fractures and ovariectomized (OVX) mice. Additionally, miR-103-3p directly targeted Mettl14 to inhibit osteoblast activity, and METTL14-dependent N-6-methyladenosine (m(6)A) methylation inhibited miR-103-3p processing by the microprocessor protein DGCR8 and promoted osteoblast activity. Moreover, miR-103-3p inhibited bone formation in vivo, and therapeutic inhibition of miR-103-3p counteracted the decreased bone formation in OVX mice. Further, METTL14 was negatively correlated with miR-103-3p but positively correlated with bone formation in bone specimens from elderly women with fractures and OVX mice. Collectively, our results highlight the critical roles of the miR-103-3p/METTL14/m(6)A signaling axis in osteoblast activity, identifying this axis as a potential target for ameliorating osteoporosis.

Automated summary

The study identified the miR-103-3p/METTL14/m(6)A signaling axis as a critical regulator of osteoblast activity, with miR-103-3p targeting Mettl14 to inhibit osteoblast function and METTL14 promoting osteoblast activity through m(6)A methylation of miR-103-3p. Therapeutic inhibition of miR-103-3p reversed the decreased bone formation, indicating the potential of this signaling axis as a target for ameliorating osteoporosis.