Cross‐Talk Between Hedgehog and PDGFRα Pathways in mMSCs Modulates Alveolar Bone Regeneration

OBJECTIVE: This study aimed to explore the roles of Hedgehog (Hh) and platelet-derived growth factor receptor α (PDGFRα) pathways in regulating osteogenic differentiation of mesenchymal stem cells (MSCs). METHODS: An alveolar bone defect model was created by extracting the first upper molars of mice. Mouse alveolar bone-derived MSCs (mMSCs) were isolated to evaluate the effects of Hh/PDGFRα pathways on osteogenic differentiation. We constructed PDGFRα short hairpin RNA plasmids to knock down PDGFRα expression, and the effects of PDGFRα knockdown on the proliferation, migration, and osteogenic differentiation of mMSCs mediated by Hh were analyzed. Gelatin sponges were used as scaffolds to deliver mMSCs into tooth extraction wounds to study the effects of Hh/PDGFRα pathways on alveolar bone regeneration. RESULTS: The Hh pathway was activated during tooth extraction wounds healing. Hh upregulated PDGFRα expression in mMSCs (p < 0.05). PDGFRα knockdown weakened Hh signaling and its ability to enhance mMSCs' proliferation and migration (p < 0.05). Additionally, PDGFRα knockdown impaired the Hh pathway's effects on osteogenic differentiation (p < 0.01) and alveolar bone regeneration (p < 0.05). CONCLUSIONS: The cross-talk of Hh/PDGFRα c regulates mMSCs' osteogenic differentiation to promote alveolar bone regeneration. Targeting Hh/PDGFRα signaling may provide intervention strategies for bone regeneration therapies.