Introduction and objective:
Delayed fracture healing (DFH) represents a frequently encountered complication in the surgical management of fractures. The aim of the study is to elucidate how miR-181a-1-3p regulates DKK2 expression.

Material and methods:
The study included 95 normal fracture healing (NFH) patients and 70 DFH patients. The expression of miR-181a-1-3p, DKK2, and osteogenic differentiation markers (RUNX2, OCN, OPN) was detected using RT-qPCR. The diagnostic utility of miR-181a-1-3p in DFH was evaluated through ROC curve. Cell proliferation was determined by CCK-8 assay. Detection of ALP activity was performed with an ELISA kit. Dual luciferase reporter assay and RIP assay were employed to validate the targeted binding of miR-181a-1-3p and DKK2.

Results:
Serum miR-181a-1-3p expression was up-regulated and DKK2 expression was down-regulated in DFH patients compared to the NFH group. miR-181a-1-3p had high diagnostic value for DFH. Inhibition of miR-181a-1-3p significantly promoted the proliferation of MC3T3-E1 cells, elevated migration, and up-regulated ALP activity and RUNX2, OCN, OPN levels. While over-expression of miR-181a-1-3p produced opposite results. DKK2 was a target gene of miR-181a-1-3p. Knockdown of DKK2 partially reversed the effects of inhibiting miR-181a-1-3p on the proliferation, migration and differentiation of MC3T3-E1 cells.

Conclusions:
miR-181a-1-3p regulates osteoblast proliferation, migration and differentiation processes by targeting DKK2, thereby affecting the pathological development of DFH. This research offers a potential theoretical foundation for the early diagnosis and targeted treatment of DFH.