Cyclic distraction–compression promotes bone regeneration during distraction osteogenesis through the Piezo1–YAP–β-catenin axis

Background Distraction osteogenesis (DO) is an effective reconstructive strategy for large bone defects, but its clinical application is constrained by slow regenerate maturation and prolonged consolidation. The cyclic distraction–compression (CDC, accordion technique) has shown promise in enhancing bone formation; however, its underlying mechanotransduction mechanisms remain poorly understood. Methods A rat femoral DO model was established and CDC was applied during the mid-consolidation phase. To interrogate mechanistic pathways, a Piezo1 agonist (Yoda1) or inhibitor (GsMTx4) was locally administered. Bone regeneration was evaluated by serial radiography, micro-computed tomography, biomechanical testing, histomorphology, and immunohistochemical analyses. Results CDC significantly enhanced regenerate bone volume, mineral density, structural continuity, and mechanical properties compared with controls. Activation of Piezo1 further amplified these effects, whereas Piezo1 inhibition attenuated CDC-induced improvements. At the molecular level, CDC increased the expression of Piezo1, YAP, and β-catenin, accompanied by elevated osteogenic markers (RUNX2, OPN) and angiogenic markers (VEGF, CD31). These findings indicate that CDC promotes coupled osteogenesis and angiogenesis within the distraction regenerate through Piezo1-dependent signaling. Conclusion Our study suggests that CDC accelerates bone regeneration during distraction osteogenesis, potentially through Piezo1–YAP–β-catenin–associated signaling and enhanced osteogenic–angiogenic coupling. These results provide mechanistic insight into the accordion technique and support the development of optimized mechanical and mechanosensory-targeted strategies to improve DO outcomes.