LncRNA MIR503HG promotes delayed fracture healing by regulating the miR-497-5p/HMGA2 axis

Delayed fracture healing (DFH) frequently occurs as a complication following a fracture. Most fractures heal successfully after surgery, but 5%-10% of patients experience delayed or non-healing, causing pain, disability, psychological issues, and economic burdens. This study aims to investigate the abnormal expression and clinical role of MIR503HG in DFH, as well as to explore the molecular mechanism by which MIR503HG affects fracture healing. This study included a cohort of 187 fracture patients, comprising 90 normal healing individuals and 97 delayed healing patients. The expression levels of MIR503HG in both serum and cellular samples were quantified utilizing RT-qPCR. The predictive capacity of MIR503HG for DFH was assessed through the construction of a ROC curve. The impact of MIR503HG on osteoclast proliferation was examined via the CCK-8 assay, while the levels of apoptosis were determined by means of flow cytometry. MIR503HG expression was elevated in the serum of DFH patients, and this heightened expression may serve as a predictive biomarker for the onset of DFH. Suppression of MIR503HG expression inhibited the proliferation and differentiation of osteoclasts while concurrently promoting cellular apoptosis. Inhibition of miR-497-5p was found to counteract the effects of MIR503HG knockdown on osteoclast proliferation, apoptosis, and differentiation markers. Moreover, MIR503HG enhances the expression of HMGA2 by directly inhibiting the expression of miR-497-5p. MIR503HG may delay fracture healing by regulating the miR-497-5p/HMGA2 axis.

The online version contains supplementary material available at 10.1007/s10616-026-00942-8.