Isopsoralen Promotes Mandibular Fracture Healing by Regulating Autophagy

Area of Science:

• Orthopedics and Traumatology
• Pharmacology
• Cell Biology

Background:

• Mandibular fractures are common maxillofacial injuries, with a significant rate of delayed union or nonunion.
• Isopsoralen (ISO), derived from Psoralea corylifolia L., possesses known osteogenic and anti-inflammatory properties.
• The precise role of autophagy in ISO-enhanced mandibular fracture healing requires elucidation.

Purpose of the Study:

• To investigate the therapeutic effects of ISO on mandibular fracture healing in a rat model.
• To explore the underlying mechanism involving autophagy modulation.

Main Methods:

• Rats with mandibular fractures were treated with ISO, 3-methyladenine (an autophagy inhibitor), or combinations.
• Fracture healing was evaluated using radiographic scoring, micro-CT, histological analysis, and biochemical assays.
• Autophagy markers (P62, Beclin-1, LC3-II/I) were assessed via Western blotting.

Main Results:

• 3-Methyladenine (3-MA) treatment impaired fracture healing, reducing bone quality and formation.
• ISO administration improved bone microarchitecture and increased serum markers of bone formation (alkaline phosphatase, osteocalcin).
• ISO modulated autophagy markers, indicating stabilization of autophagic flux, which was partially reversed by 3-MA.

Conclusions:

• Isopsoralen (ISO) demonstrates a positive effect on mandibular fracture healing in rats.
• ISO appears to exert its beneficial effects by regulating and stabilizing autophagic flux.
• These findings suggest ISO as a potential therapeutic agent for delayed or nonunion bone fractures.