<p>To explore the predictive value of miR-451-5p in delayed fracture healing (DFH) and its mechanism of action in fracture healing. Patients with normal fracture healing (NFH) and DFH were included in this study. The expression of miR-451-5p in serum was detected by RT-qPCR. The predictive potential of miR-451-5p for DFH was evaluated by ROC analysis, and risk factors influencing DFH were determined using logistic regression analysis. The proliferation, apoptosis and expression levels of osteogenic differentiation markers (ALP, BMP2, OSX) of mouse embryonic osteoblast precursor cells (MC3T3-E1) were detected by CCK-8, flow cytometry, RT-qPCR and western blot. The targeting relationship between miR-451-5p and ATF2 was verified by dual-luciferase reporter assay and RNA pull-down experiments. The level of miR-451-5p in the serum of DFH patients was significantly higher than that in the NFH group. Its sensitivity for predicting DFH was 81.33%, and its specificity was 86.96%. miR-451-5p is an independent risk factor for DFH. Overexpression of miR-451-5p could inhibit the proliferation of osteogenic precursor cells, promote cell apoptosis, and downregulate the expression of osteogenic differentiation markers. miR-451-5p binds to ATF2 and inhibits its expression. Overexpression of ATF2 could reverse the inhibitory effect of miR-451-5p on osteogenic differentiation. During the process of osteogenesis, miR-451-5p negatively regulates cell proliferation and osteogenesis by inhibiting the function of ATF2. Clinically, miR-451-5p has the potential to serve as a biomarker for the early predictive of DFH.</p>