State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Oral Diseases, Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
Department of Stomatology, The Affiliated Shenzhen Maternity and Child Healthcare Hospital of the South Medical University, Shenzhen, Guangdong, 518048, China.
Sci Rep. 2017 Jul 12;7(1):5254. doi: 10.1038/s41598-017-05762-7.
Inflammatory microenvironment causes the change of epigenetic modification in periodontal ligament stem cells derived from periodontitis tissues (P-PDLSCs), which results in defective osteogenic differentiation compared to cells from healthy tissues. It's urgent to explore therapeutic strategies aimed at epigenetic targets associated with the regenerative ability of PDLSCs. Osthole, a small-molecule compound extracted from Chinese herbs, has been documented to promote osteogenesis and cell sheets formation of healthy PDLSCs. However, whether osthole shows same effect on P-PDLSCs and the mechanism of promotive effect is still unknown. The purpose of this study was to determine whether Osthole could restore defective osteogenic differentiation of P-PDLSCs via epigenetic modification. We demonstrated that 10 Mol/L of Osthole was the best concentration for osteogenic differentiation and proliferation of P-PDLSCs. Mechanistically, we also found that Osthole upregulated MOZ and MORF, histone acetylases that specifically catalyze acetylation of Histone3 lisine9 (H3K9) and Histone3 lisine14 (H3K14), which are key regulators in osteogenic differentiation of P-PDLSCs. Furthermore, Osthole treatment improved cell sheet formation and enhanced the bone formation of PDLSC sheets in animal models of periodontitis. Our study suggests that Osthole is a promising drug to cure periodontitis via regulating epigenetic modification in cell sheets engineering.
炎症微环境导致牙周炎组织来源的牙周韧带干细胞（P-PDLSCs）中表观遗传修饰的改变，这导致其成骨分化缺陷，与来自健康组织的细胞相比。探索针对与 PDLSCs 再生能力相关的表观遗传靶点的治疗策略迫在眉睫。蛇床子素是一种从中药中提取的小分子化合物，已被证明可促进健康 PDLSCs 的成骨作用和细胞片形成。然而，蛇床子素是否对 P-PDLSCs 具有相同的作用，以及促进作用的机制尚不清楚。本研究旨在确定蛇床子素是否可以通过表观遗传修饰来恢复 P-PDLSCs 的成骨分化缺陷。我们证明，10μmol/L 的蛇床子素是促进 P-PDLSCs 成骨分化和增殖的最佳浓度。从机制上讲，我们还发现蛇床子素上调了 MOZ 和 MORF，这两种组蛋白乙酰转移酶特异性催化组蛋白 3 赖氨酸 9（H3K9）和组蛋白 3 赖氨酸 14（H3K14）的乙酰化，这是 P-PDLSCs 成骨分化的关键调节因子。此外，蛇床子素处理可改善细胞片的形成，并增强牙周炎动物模型中 PDLSC 片的骨形成。我们的研究表明，蛇床子素是一种很有前途的药物，可通过调节细胞片工程中的表观遗传修饰来治疗牙周炎。
