Schisantherin A promotes neural differentiation of stem cells from apical papilla to improve mandibular development via mental nerve repair.

BACKGROUND

Evidence shows neural involvement in bone remodeling; regulating maxillofacial nerve repair modulates jawbone. Neural stem cell (NSC) therapy is limited by sources/ethics, but neural crest-derived dental mesenchymal stem cells (MSCs) like stem cells from the apical papilla (SCAPs) have strong neuroregenerative potential for NSC transdifferentiation. Schisantherin A (Sch-A), neuroprotective, enhances NSC proliferation/differentiation. This study explores optimal Sch-A concentration/duration for SCAP neural differentiation and effects on rat mental nerve repair/mandibular development.

METHODS

SCAPs' mesenchymal stem cell properties were verified via flow cytometry and trilineage differentiation. Effects of different Sch-A concentrations were evaluated using CCK-8, colony formation, scratch assay, qRT-PCR, immunofluorescence, and Western blot. Transcriptome sequencing identified underlying mechanisms and determined optimal. A mental nerve injury model was established in 4-week-old SD rats (five groups; n = 4 per group) to assess neurorepair, functional recovery, and mandibular development following transplantation of Sch-A-induced SCAPs.

RESULTS

Treatment with 10- 9 mol/L Sch-A for 1 week induced robust neural differentiation in SCAPs, with high expression of nestin and NSE. Mental nerve-injured SD rats exhibited reduced lip sensation, abnormal nerve morphology, and inhibited transverse development of the anterior mandibular. Transcriptome analysis revealed Sch-A primarily acts via neuroactive ligand-receptor interaction pathway. Transplantation of induced SCAPs promoted nerve repair and restored mandibular development.

CONCLUSION

Sch-A at 10- 9 mol/L concentration promotes the transdifferentiation of SCAPs into neural stem cell-like cells primarily through the neuroactive ligand-receptor interaction pathway. These Sch-A induced SCAPs effectively repair mental nerve injury and facilitate normal mandibular development.