Epigenetic modifier trichostatin A enhanced osteogenic differentiation of mesenchymal stem cells by inhibiting NF-κB (p65) DNA binding and promoted periodontal repair in rats
Epigenetic modifier trichostatin A enhanced osteogenic differentiation of mesenchymal stem cells by inhibiting NF-κB (p65) DNA binding and promoted periodontal repair in rats
复制标题
表观遗传修饰剂曲古抑菌素 A 通过抑制 NF-κ B (p65) DNA 结合增强间充质干细胞的成骨分化并促进大鼠牙周修复
DOI：
10.1002/jcp.29780
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发表时间：
2020-05-12
影响因子：
5.6
通讯作者：
Liu, Dayong
中科院分区：
文献类型：
--
作者：
Li, Qiong;Liu, Fan;Liu, Dayong
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。我们从健康和发炎的牙龈组织中分离出MSC，以研究在体外，阿司他丁A（TSA）是否可以促进成骨分化和解决炎症。在大鼠牙周炎模型中，用温度依赖性的壳聚糖支架包封的TSA治疗时，评价组织再生潜力。条件培养基诱导后，TSA处理增加了发炎MSC和健康MSC的成骨分化潜能。此外，TSA处理后上清液中的白细胞介素-6和白细胞介素-8水平显著降低。此外，TSA通过抑制核因子-κ B（p65）DNA结合促进MSCs的成骨分化。在实验性牙周炎大鼠中，局部注射壳聚糖支架包封的TSA后7周，组织学和显微计算机断层扫描显示，与溶剂治疗的大鼠相比，牙槽骨体积显著增加，炎症浸润减少。TSA治疗后，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潜在治疗选择。
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-kappa B (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-gamma 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.