Wnt/OPG signaling axis drives ectopic mandibular regeneration: Mechanism mediated by tibial periosteal stem cell sheets.

Mandibular reconstruction presents substantial clinical challenges due to the jaw's complex anatomical and functional requirements. This study investigated gene expression differences between tibial and mandibular periosteum to understand their distinct osteogenic properties and evaluate the therapeutic potential of tibial periosteum-derived stem cell (PSC) sheets for mandibular defect repair.Transcriptomic analysis revealed differential expression patterns: tibial periosteum demonstrated higher OPG expression, while mandibular periosteum exhibited increased RUNX2 and BMP-2 expression. KEGG enrichment analysis identified the Wnt signaling pathway as a key regulatory mechanism. To test this therapeutic approach, we cultured rat tibial PSCs into cell sheets and implanted them into mandibular defects, then assessed bone regeneration through micro-CT, histological examination, and immunohistochemistry.The results demonstrated that tibial PSC sheet implantation significantly enhanced bone volume, trabecular thickness, collagen deposition, and expression of osteogenic markers in mandibular defects. Notably, inhibition of Wnt signaling through DKK1 markedly suppressed mineralization and osteogenesis, confirming this pathway's critical role in the regenerative process.These findings establish that tibial PSC sheets promote mandibular bone repair through dual mechanisms: Wnt-mediated osteogenesis and OPG-driven anti-resorption activity. This combination provides sustained bone regeneration and represents a promising therapeutic strategy for mandibular reconstruction, demonstrating the feasibility of utilizing tibial periosteum-derived cells to overcome the inherent limitations of mandibular periosteum in bone repair applications.