Abstract
BACKGROUND: Pilon fractures are high-energy injuries often associated with delayed healing after treatment. MiR-3651 is a short non-coding RNA, yet its expression level, therapeutic effect, and specific mechanism in the healing process of Pilon fractures remain unclear. AIM: This study investigates the association between miR-3651 expression and Pilon fracture healing, assesses its diagnostic utility, and elucidates its regulatory mechanism. METHODS: The expression levels of miR-3651, KRAS, and osteoclast differentiation markers were detected using RT-qPCR. The diagnostic efficacy of miR-3651 for delayed healing of Pilon fractures was assessed via ROC curve analysis, and logistic regression was employed to identify risk factors influencing delayed healing. Cell viability and apoptosis were measured using the CCK-8 assay and flow cytometry. The targeting relationship between miR-3651 and KRAS was verified through the dual-luciferase reporter assay. RESULTS: MiR-3651 expression was significantly upregulated in the delayed healing group, with concomitant downregulation of its downstream target KRAS. MiR-3651 effectively distinguished between normal healing and delayed healing and was identified as a risk factor influencing the occurrence of delayed healing. Inhibition of miR-3651 expression reduced osteoclast activity and differentiation while promoting apoptosis; conversely, overexpression of miR-3651 produced the opposite effects. Knockdown of KRAS expression reversed the impact of miR-3651 inhibition on osteoclast activity, apoptosis, and differentiation. CONCLUSIONS: Downregulation of miR-3651 expression inhibits osteoclast formation, and knockdown of KRAS restores this inhibitory effect.