miR-34a-5p targets Foxp1 to promote osteoclast differentiation and accelerate fracture healing

Abstract Fracture healing is an intricate biological process that is dependent on osteoblast differentiation. MicroRNAs (miRNAs) regulate gene expression post-transcriptionally, and these molecules participate in osteoblast regulation in bone-related diseases; however, the role of miR-34a-5p in osteoblast differentiation during fracture healing remains unclear. In this study, miR-34a-5p expression during osteoblast differentiation and its functional effects on MC3T3-E1 cells were examined. Overexpression of miR-34a-5p promoted osteoblast differentiation by upregulating the expression of markers such as Runx2, Osx, Opn, and Ocn, while inhibiting osteoclast differentiation. Moreover, alkaline phosphatase and alizarin red staining confirmed enhanced mineralization. Mechanistically, miR-34a-5p directly targeted and suppressed Foxp1, a negative regulator of osteoblast differentiation. In vivo, miR-34a-5p mimics accelerated fracture healing, whereas Foxp1 overexpression inhibited osteoblast differentiation, and this effect was reversed by miR-34a-5p. These findings suggest that miR-34a-5p promotes fracture healing by targeting Foxp1, which could provide a potential therapeutic target for nonunion fractures.