Effect of metformin on human periodontal ligament stem cells cultured with polydopamine-templated hydroxyapatite
Effect of metformin on human periodontal ligament stem cells cultured with polydopamine-templated hydroxyapatite
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二甲双胍对聚多巴胺模板羟基磷灰石培养人牙周膜干细胞的影响
DOI：
10.1111/eos.12616
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发表时间：
2019
影响因子：
1.9
通讯作者：
Song Jinlin
中科院分区：
文献类型：
--
作者：
Yang Zun;Gao Xiang;Zhou Mengjiao;Kuang Yunchun;Xiang Mingli;Li Jie;Song Jinlin
聚多巴胺模板羟基磷灰石（tHA）是一种纳米生物材料，可促进骨组织工程中的成骨。然而，高浓度的tHA刺激活性氧（ROS）的产生，导致细胞损伤和凋亡。已证明二甲双胍激活腺苷一磷酸活化蛋白激酶（AMPK）信号通路，其诱导自噬并减少ROS产生以防止细胞凋亡。本研究旨在探讨tHA联合二甲双胍在牙周骨组织工程中的潜在应用。将人牙周膜干细胞（hPDLSCs）在二甲双胍存在或不存在的情况下暴露于tHA，并通过相关试验检测细胞相容性和成骨作用。此外，通过蛋白质印迹分析自噬信号通路。聚多巴胺模板羟基磷灰石与二甲双胍联合使用，可显著降低ROS产生和细胞凋亡，并增强hPDLSC的增殖和成骨分化。暴露于tHA+二甲双胍后，观察到微管相关蛋白1轻链3 II和Beclin-1水平升高。暴露于tHA加二甲双胍后，磷酸化AMPK的表达增加，磷酸化哺乳动物雷帕霉素靶蛋白（mTOR）的表达减少。综上所述，我们的结果表明，tHA与二甲双胍组合通过AMPK/mTOR信号通路调节自噬并进一步改善成骨作用，从而增加hPDLSC的活力。
Polydopamine‐templated hydroxyapatite (tHA) is a type of nano‐biomaterial that can promote osteogenesis in bone tissue engineering. However, high concentrations of tHA stimulate production of reactive oxygen species (ROS), resulting in cell injury and apoptosis. Metformin has been demonstrated to activate the adenosine monophosphate‐activated protein kinase (AMPK) signaling pathway, which induces autophagy and decreases ROS production to prevent apoptosis. The present study was performed to investigate the potential application of tHA in combination with metformin in periodontal bone tissue engineering. Human periodontal ligament stem cells (hPDLSCs) were exposed to tHA in the presence or absence of metformin, and cytocompatibility and osteogenesis were detected by related assays. Additionally, the autophagy signaling pathway was analyzed by western blotting. Polydopamine‐templated hydroxyapatite, in combination with metformin, substantially reduced ROS production and apoptosis, and enhanced proliferation and osteogenic differentiation of hPDLSCs. Enhanced levels of microtubule‐associated protein 1 light chain 3 II and Beclin‐1 were observed after exposure to tHA plus metformin. Expression of phosphorylated AMPK was increased and that of phosphorylated mammalian target of rapamycin (mTOR) was decreased after exposure to tHA plus metformin. Taken together, our results demonstrate that tHA, combined with metformin, increases the viability of hPDLSCs via the AMPK/mTOR signaling pathway by regulating autophagy and further improving the osteogenic effect.