State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China; Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China; Department of Orthodontics, Stomatological Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an 710004, China.
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China; State Key Laboratory of Oral Disease, West China School of Stomatology, Sichuan University, Chengdu 610041, China.
Acta Biomater. 2022 Mar 15;141:333-343. doi: 10.1016/j.actbio.2021.12.035. Epub 2022 Jan 1.
Periodontitis is the primary cause of tooth loss, but there is no effective treatment to repair inflammatory bone loss in periodontitis. Exosomes emerge as essential paracrine factors of mesenchymal stem cells (MSCs) that mediated tissue regeneration. Here, we investigated the potential of exosomes secreted by periodontal ligament stem cells (PDLSCs) as therapeutics for the bone defect in periodontitis. Exosomes secreted from PDLSCs derived from healthy periodontal ligaments (h-PDLSCs) and their function were evaluated on PDLSCs isolated from the inflammatory periodontal ligament of periodontitis patients (i-PDLSCs). Treatment of exosomes of h-PDLSCs led to an increase in the formation of mineralized nodules and the expressions of osteogenic genes and proteins in i-PDLSCs. Mechanistically, h-PDLSCs-exosomes suppressed the over-activation of canonical Wnt signaling to recover the osteogenic differentiation capacity of i-PDLSCs. To evaluate the therapeutic of exosomes on inflammatory bone loss, h-PDLSCs-exosomes loaded with Matrigel or β-TCP were employed to repair bone defects in rat models of periodontitis. Compared to the vehicle-treated control group, h-PDLSCs-exosomes-treated rats resulted in more bone formation in the defect of alveolar bone. In conclusion, these results demonstrated that exosomes derived from healthy PDLSCs could rescue the osteogenesis capacity of endogenous stem cells under an inflammatory environment and promote regeneration of alveolar bone. Our findings suggest that MSCs-derived exosome is an effective and practical cell-free MSC therapeutic for the treatment of periodontitis. STATEMENT OF SIGNIFICANCE: There is no effective treatment to repair inflammatory bone loss in periodontitis. As essential paracrine factors of PDLSCs, exosomes might mediate tissue regeneration during stem cell therapy. Here, we reported that exosomes secreted from healthy PDLSCs promoted the osteogenic differentiation of PDLSCs derived from periodontitis tissue. Healthy PDLSCs-exosomes treatment resulted in accelerated bone formation in the defect of alveolar bone in rat models of periodontitis. Mechanistically, h-PDLSCs-exosomes suppressed the over-activation of canonical Wnt signaling to recover the osteogenic differentiation capacity of inflammatory PDLSCs. These findings suggest that MSCs-derived exosome is an effective and practical cell-free MSC therapeutic for the treatment of periodontitis.
牙周炎是牙齿缺失的主要原因，但目前尚无有效治疗方法来修复牙周炎的炎症性骨损失。外泌体作为间充质干细胞（MSCs）的重要旁分泌因子出现，介导组织再生。在这里，我们研究了牙周韧带干细胞（PDLSCs）分泌的外泌体作为治疗牙周炎骨缺损的潜在治疗方法。从健康牙周韧带（h-PDLSCs）衍生的外泌体及其功能在从牙周炎炎症性牙周韧带分离的 PDLSCs（i-PDLSCs）上进行了评估。h-PDLSCs 来源的外泌体处理导致矿化结节的形成增加和 i-PDLSCs 中成骨基因和蛋白的表达增加。在机制上，h-PDLSCs 外泌体抑制了经典 Wnt 信号的过度激活，恢复了 i-PDLSCs 的成骨分化能力。为了评估外泌体对炎症性骨丢失的治疗作用，将负载 Matrigel 或β-TCP 的 h-PDLSCs 外泌体用于修复牙周炎大鼠模型中的骨缺损。与仅用载体处理的对照组相比，h-PDLSCs 外泌体处理的大鼠在牙槽骨缺损处形成了更多的骨。总之，这些结果表明，来自健康 PDLSCs 的外泌体可以在炎症环境下挽救内源性干细胞的成骨能力，并促进牙槽骨的再生。我们的研究结果表明，MSCs 衍生的外泌体是一种有效的、实用的无细胞 MSC 治疗方法，可用于治疗牙周炎。
