Osthole improves function of periodontitis periodontal ligament stem cells via epigenetic modification in cell sheets engineering.
Osthole improves function of periodontitis periodontal ligament stem cells via epigenetic modification in cell sheets engineering.
复制标题
蛇床子素通过细胞片工程表观遗传修饰改善牙周炎牙周膜干细胞的功能
DOI：
10.1038/s41598-017-05762-7
复制
发表时间：
2017-07-12
影响因子：
4.6
通讯作者：
Jin Y
中科院分区：
文献类型：
--
作者：
Sun J;Dong Z;Zhang Y;He X;Fei D;Jin F;Yuan L;Li B;Jin Y
炎症微环境导致牙周炎组织来源的牙周膜干细胞（P-PDLSCs）表观遗传修饰发生改变，导致其向成骨细胞的分化能力低于健康组织来源的细胞。因此，迫切需要探索针对与PDLSCs再生能力相关的表观遗传靶点的治疗策略。蛇床子素是一种从中草药中提取的小分子化合物，已被证明可以促进健康PDLSCs的成骨和细胞片层形成。然而，蛇床子素是否对P-PDLSCs具有同样的作用，其促进作用的机制尚不清楚。本研究的目的是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，10−7 Mol/L的蛇床子素是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MOZ和MORF，MOZ和MORF是特异性催化组蛋白3赖氨酸9（H3 K9）和组蛋白3赖氨酸14（H3 K14）乙酰化的组蛋白乙酰化酶，它们是P-PDLSC成骨分化的关键调节因子。此外，蛇床子素处理改善牙周炎动物模型中PDLSC片的细胞片形成并增强其骨形成。我们的研究表明，Osthole是一种通过调节细胞片工程中的表观遗传修饰来治疗牙周炎的有前途的药物。
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 10−7 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.
登录
查看更多内容
影响因子：
3.7
作者：
Imamura, T;Kakazu, N;Imashuku, S
通讯作者：
Imashuku, S
影响因子：
8
作者：
Pelletier, N;Champagne, N;Yang, XJ
通讯作者：
Yang, XJ
影响因子：
7.6
作者：
Martins, M. D.;Jiao, Y.;Castilho, R. M.
通讯作者：
Castilho, R. M.
DOI：
10.3390/molecules20058000
发表时间：
2015-05-04
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Pai JT;Hsu CY;Hua KT;Yu SY;Huang CY;Chen CN;Liao CH;Weng MS
通讯作者：
Weng MS
抑制组蛋白脱乙酰酶可增强小鼠间充质干细胞中 BMP9 诱导的成骨信号传导
影响因子：
--
作者：
Hu, Ning;Wang, Changdong;Huang, Wei
通讯作者：
Huang, Wei