Periodontal ligament stem cell-derived exosomes promote alveolar bone defect repair in periodontitis by mediating M2 macrophage polarization via regulation of the SEMA4D/PLXNB1 axis

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Periodontal ligament stem cell-derived exosomes promote alveolar bone defect repair in periodontitis by mediating M2 macrophage polarization via regulation of the SEMA4D/PLXNB1 axis
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Keywords

Alveolar bone loss
Bone regeneration
Macrophage polarization
Periodontal ligament
Periodontitis
Plexin B1
Semaphorin 4D
Signal transduction
Sprague-Dawley
Stem cells
Tissue repair

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Yang Y, Zhang C. Periodontal ligament stem cell-derived exosomes promote alveolar bone defect repair in periodontitis by mediating M2 macrophage polarization via regulation of the SEMA4D/PLXNB1 axis. Electron. J. Biotechnol. [Internet]. 2026 May 15 [cited 2026 Jun. 2];81:100712. Available from: https://www.ejbiotechnology.info/index.php/ejbiotechnology/article/view/2548

Abstract

Background: Periodontitis is a chronic inflammatory disease characterized by progressive alveolar bone loss. This study explored the role of exosomes derived from periodontal ligament stem cells (PDLSCs-Exo) in repairing alveolar bone defects in periodontitis.

Results: PDLSCs-Exo significantly promoted new bone formation and collagen deposition in the defect area while reducing pro-inflammatory factors and enhancing M2 macrophage polarization. The knockdown of semaphorin 4D (SEMA4D) or plexin B1 (PLXNB1) further enhanced exosome-mediated repair, whereas their overexpression attenuated it. Additionally, the upregulation of PLXNB1 reversed the reparative effects of SEMA4D downregulation on alveolar bone defects in periodontitis.

Conclusions: PDLSCs-Exo promotes M2 macrophage polarization by inhibiting the SEMA4D/PLXNB1 axis, alleviating local inflammation and accelerating alveolar bone defect repair in periodontitis. This finding provides a novel theoretical basis for the clinical treatment of periodontitis-related alveolar bone defects and identifies potential therapeutic targets for improving the efficacy of bone defect repair.

https://doi.org/10.1016/j.ejbt.2026.100712
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