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

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.