Department of Endodontics & Laboratory for Dental Stem Cells and Endocrine Immunology, Tianjin Medical University School of Stomatology, Tianjin, China.
Institute of Oral Medicine Research, Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China.
J Cell Physiol. 2020 Dec;235(12):9691-9701. doi: 10.1002/jcp.29780. Epub 2020 May 12.
We wished to evaluate whether epigenetic modifiers have a beneficial effect on treating experimental periodontitis and mechanisms for regulating the cell fate of mesenchymal stem cells (MSCs) in inflammatory microenvironments. We isolated MSCs from healthy and inflamed gingival tissues to investigate whether trichostatin A (TSA) could improve osteogenic differentiation and resolve inflammation in vitro. The tissue regenerative potentials were evaluated when treated with a temperature-dependent, chitosan-scaffold-encapsulated TSA, in a rat model of periodontitis. After induction with the conditioned medium, TSA treatment increased the osteogenic differentiation potential of inflamed MSCs and healthy MSCs. In addition, interleukin-6 and interleukin-8 levels in supernatants were significantly decreased after TSA treatment. Moreover, TSA promoted osteogenic differentiation by inhibiting nuclear factor-κB (p65) DNA binding in MSCs. In rats with experimental periodontitis, 7 weeks after local injections of chitosan-scaffold-encapsulated TSA, histology and microcomputed tomography showed a significant increase in alveolar bone volume and less inflammatory infiltration compared with vehicle-treated rats. The concentrations of interferon-γ and interleukin-6 were significantly decreased in the gingival crevicular fluid after TSA treatment. This study demonstrated that TSA had anti-inflammatory properties and could promote periodontal tissue repair, which indicated that epigenetic modifiers hold promise as a potential therapeutic option for periodontal tissue repair.
我们希望评估表观遗传修饰剂是否对治疗实验性牙周炎具有有益作用，以及它们在炎症微环境中调节间充质干细胞 (MSC) 细胞命运的机制。我们从健康和炎症牙龈组织中分离 MSC，以研究曲古抑菌素 A (TSA) 是否可以改善体外成骨分化和缓解炎症。当用温度依赖性壳聚糖支架包封的 TSA 处理时，在牙周炎大鼠模型中评估组织再生潜力。在诱导条件培养基后，TSA 处理增加了炎症 MSC 和健康 MSC 的成骨分化潜能。此外，TSA 处理后上清液中白细胞介素-6 和白细胞介素-8 水平显著降低。此外，TSA 通过抑制 MSC 中核因子-κB (p65) DNA 结合来促进成骨分化。在牙周炎大鼠模型中，局部注射壳聚糖支架包封 TSA 7 周后，与载体处理的大鼠相比，组织学和微计算机断层扫描显示牙槽骨体积明显增加，炎症浸润减少。TSA 处理后龈沟液中干扰素-γ 和白细胞介素-6 的浓度显著降低。这项研究表明，TSA 具有抗炎特性，可以促进牙周组织修复，这表明表观遗传修饰剂有望成为牙周组织修复的一种潜在治疗选择。
