Hh/Pdgfrα Pathways Enhance Mmscs Osteogenesis For Alveolar Regeneration

Aim or purpose: Alveolar bone defects caused by trauma, tumors, or periodontal disease are challenging in clinical oral medicine. Mesenchymal stem cells (MSCs) transplantation is a promising bone regeneration therapy. The Hedgehog (Hh) and platelet-derived growth factor receptor α (PDGFRα) pathways are closely associated with the multilineage differentiation of MSCs. This study explores the role of Hh/PDGFRα signaling pathways in MSCs osteogenic differentiation and alveolar bone regeneration. Materials and methods: Establishment of mouse alveolar bone defect model and detection of signaling molecules and osteogenesis-related factors at different healing time points. Mouse alveolar bone-derived MSCs (mMSCs) were cultured and characterized. The regulatory effects of the Hh pathway on osteogenic differentiation were assessed using Hh agonist N-Shh and antagonist Gant61. Flow cytometry, immunofluorescence were used to investigate the interaction in Hh/PDGFRα signaling. The role of Hh/PDGFRα signaling in alveolar bone regeneration was evaluated using micro-computed tomography and histological staining. Results: During alveolar bone healing, Hh/PDGFRα signaling molecules and osteogenic factors were upregulated synchronously. N-Shh increased calcium nodule formation and ALP expression in mMSCs, while Gant61 had the opposite effect. N-Shh promoted PDGFRα expression, and PDGFRα knockdown downregulated Hh pathway molecules, inhibiting Hh signaling-mediated proliferation, migration, and osteogenic differentiation of mMSCs. In vivo transplantation confirmed that PDGFRα knockdown partially inhibited Hh signaling-mediated osteogenic effects on alveolar bone regeneration. Conclusions: Hh/PDGFRα pathways enhances the osteogenic differentiation of mMSCs and promotes alveolar bone regeneration. Targeting the Hh/PDGFRα pathway may provide a therapeutic strategy for alveolar bone defect treatment.