Department of Endodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, 401147, People's Republic of China.
Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, 401147, People's Republic of China.
Int J Nanomedicine. 2023 Aug 17;18:4683-4703. doi: 10.2147/IJN.S420967. eCollection 2023.
Dental pulp stem cell-derived exosomes (DPSC-EXO), which have biological characteristics similar to those of metrocytes, have been found to be closely associated with tissue regeneration. Periodontitis is an immune inflammation and tissue destructive disease caused by plaque, resulting in alveolar bone loss and periodontal epithelial destruction. It is not clear whether DPSC-EXO can be used as an effective therapy for periodontal regeneration. The purpose of this study was not only to verify the effect of DPSC-EXO on reducing periodontitis and promoting periodontal tissue regeneration, but also to reveal the possible mechanism.
DPSC-EXO was isolated by ultracentrifugation. Then it characterized by transmission electron microscope (TEM), nanoparticle tracking analysis (NTA) and Western Blot. In vitro, periodontal ligament stem cells (PDLSCs) were treated with DPSC-EXO, the abilities of cell proliferation, migration and osteogenic potential were evaluated. Furthermore, we detected the expression of IL-1β, TNF-αand key proteins in the IL-6/JAK2/STAT3 signaling pathway after simulating the inflammatory environment by LPS. In addition, the effect of DPSC-EXO on the polarization phenotype of macrophages was detected. In vivo, the experimental periodontitis in rats was established and treated with DPSC-EXO or PBS. After 4 weeks, the maxillae were collected and detected by micro-CT and histological staining.
DPSC-EXO promoted the proliferation, migration and osteogenesis of PDLSCs in vitro. DPSC-EXO also regulated inflammation by inhibiting the IL-6/JAK2/STAT3 signaling pathway during acute inflammatory stress. In addition, the results showed that DPSC-EXO could polarize macrophages from the M1 phenotype to the M2 phenotype. In vivo, we found that DPSC-EXO could effectively reduce alveolar bone loss and promote the healing of the periodontal epithelium in rats with experimental periodontitis.
DPSC-EXO plays an important role in inhibiting periodontitis and promoting tissue regeneration. This study provides a promising acellular therapy for periodontitis.
牙髓干细胞衍生的外泌体（DPSC-EXO）具有与基质细胞相似的生物学特性，与组织再生密切相关。牙周炎是一种由斑块引起的免疫炎症和组织破坏性疾病，导致牙槽骨丧失和牙周上皮破坏。目前尚不清楚 DPSC-EXO 是否可用于牙周再生的有效治疗。本研究的目的不仅是验证 DPSC-EXO 减少牙周炎和促进牙周组织再生的效果，还要揭示其可能的机制。
通过超速离心法分离 DPSC-EXO。然后通过透射电子显微镜（TEM）、纳米颗粒跟踪分析（NTA）和 Western Blot 进行鉴定。在体外，用 DPSC-EXO 处理牙周韧带干细胞（PDLSCs），评估细胞增殖、迁移和成骨潜能。此外，我们通过 LPS 模拟炎症环境检测了 IL-1β、TNF-α和 IL-6/JAK2/STAT3 信号通路中的关键蛋白的表达。此外，还检测了 DPSC-EXO 对巨噬细胞极化表型的影响。在体内，建立大鼠实验性牙周炎模型并给予 DPSC-EXO 或 PBS 处理。4 周后，收集上颌骨进行 micro-CT 和组织学染色检测。
DPSC-EXO 促进 PDLSCs 的体外增殖、迁移和成骨。DPSC-EXO 在急性炎症应激过程中通过抑制 IL-6/JAK2/STAT3 信号通路来调节炎症。此外，结果表明 DPSC-EXO 可以将巨噬细胞从 M1 表型极化为 M2 表型。在体内，我们发现 DPSC-EXO 可以有效减少牙槽骨丧失并促进实验性牙周炎大鼠牙周上皮的愈合。
DPSC-EXO 在抑制牙周炎和促进组织再生方面发挥着重要作用。本研究为牙周炎提供了一种有前途的非细胞治疗方法。
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