Wnt/OPG信号轴驱动异位下颌骨再生：胫骨骨膜干细胞片介导的机制
Wnt/OPG signaling axis drives ectopic mandibular regeneration: Mechanism mediated by tibial periosteal stem cell sheets.
摘要(中文译文)
下颌骨重建由于颌骨复杂的解剖结构和功能需求而面临重大临床挑战。本研究探讨了胫骨骨膜与下颌骨骨膜之间的基因表达差异，以了解其不同的成骨特性，并评估胫骨骨膜来源干细胞（PSC）膜片用于下颌骨缺损修复的治疗潜力。转录组分析揭示了差异表达模式：胫骨骨膜表现出较高的OPG表达，而下颌骨骨膜则表现出RUNX2和BMP-2表达升高。KEGG富集分析确定Wnt信号通路为关键调控机制。为验证该治疗方法，我们将大鼠胫骨PSC培养为细胞膜片并植入下颌骨缺损处，随后通过micro-CT、组织学检查和免疫组织化学评估骨再生情况。结果表明，胫骨PSC膜片植入显著增强了下颌骨缺损处的骨体积、骨小梁厚度、胶原沉积以及成骨标志物的表达。值得注意的是，通过DKK1抑制Wnt信号通路可显著抑制矿化和成骨，证实了该通路在再生过程中的关键作用。这些发现表明，胫骨PSC膜片通过双重机制促进下颌骨修复：Wnt介导的成骨作用和OPG驱动的抗吸收活性。这种组合提供了持续的骨再生，代表了一种有前景的下颌骨重建治疗策略，证明了利用胫骨骨膜来源细胞克服下颌骨骨膜在骨修复应用中固有局限性的可行性。
Abstract
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.
如何引用
AMA
Liangchong Huang, Rongju Xie, Jiantong Pu, Shengjie Shao, Weihong Wang. Wnt/OPG signaling axis drives ectopic mandibular regeneration: Mechanism mediated by tibial periosteal stem cell sheets.. Tissue & cell. 2026; doi:10.1016/j.tice.2026.103542.
APA
Liangchong Huang, Rongju Xie, Jiantong Pu, Shengjie Shao, Weihong Wang (2026). Wnt/OPG signaling axis drives ectopic mandibular regeneration: Mechanism mediated by tibial periosteal stem cell sheets.. Tissue & cell. https://doi.org/10.1016/j.tice.2026.103542
GB/T 7714
Liangchong Huang, Rongju Xie, Jiantong Pu, Shengjie Shao, Weihong Wang. Wnt/OPG signaling axis drives ectopic mandibular regeneration: Mechanism mediated by tibial periosteal stem cell sheets.[J]. Tissue & cell, 2026 doi:10.1016/j.tice.2026.103542.
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