Isopsoralen Promotes Mandibular Fracture Healing by Regulating Autophagy

Background:Mandibular fractures account for 40% to 65% of maxillofacial injuries, with about 10% developing delayed union or nonunion.Isopsoralen (ISO), a main active component of Psoralea corylifolia L., exhibits osteogenic and anti-inflammatory effects.However, the role of autophagy in ISO-promoted mandibular fracture healing remains unclear.This study aimed to investigate the effects of ISO on mandibular fracture healing in rats and its underlying autophagy-mediated mechanism. Material/Methods:Specific pathogen-free-grade rats with left mandibular fractures were randomly assigned to 4 groups: normal saline (NS), ISO, 3-methyladenine (3-MA), and ISO + 3-MA.Interventions were given every 2 days.Fracture healing was assessed at 2, 4, and 6 weeks using the Lane-Sandhu radiographic scoring system, micro-computed tomography, hematoxylin-eosin staining, enzyme-linked immunosorbent assay, and western blotting. Results:Compared with other groups, the 3-MA group showed impaired healing, with lower radiographic scores, bone volume/total volume, bone mineral density, and trabecular number; higher trabecular separation; and sparse bone formation (all P < 0.05).Relative to the NS group, the ISO group exhibited improved bone microarchitecture, elevated serum alkaline phosphatase and osteocalcin levels, and distinct autophagy marker changes (at 2 weeks: upregulated sequestosome 1 (P62), downregulated microtubule-associated protein 1 light chain 3 II/I (LC3-II/I); at 6 weeks: downregulated P62, Beclin-1, and LC3II/I; all P < 0.05).Autophagy indices in the ISO + 3-MA group were comparable to those in the ISO group (P > 0.05). Conclusions:ISO stabilized autophagic flux and alleviated 3-MA-induced delayed mandibular fracture healing by regulating autophagy.