Carbon dots enhance extracellular matrix secretion for dentin-pulp complex regeneration through PI3K/Akt/mTOR pathway-mediated activation of autophagy.

Carbon dots enhance extracellular matrix secretion for dentin-pulp complex regeneration through PI3K/Akt/mTOR pathway-mediated activation of autophagy.
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碳点通过 PI3K/Akt/mTOR 通路介导的自噬激活增强细胞外基质分泌,促进牙本质牙髓复合体再生

DOI:
10.1016/j.mtbio.2022.100344
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发表时间:
2022-12
影响因子:
8.2
通讯作者:
Sun, Hongchen
Sun, Hongchen
中科院分区:
工程技术1区
文献类型:
--
作者:
Liu, Lili;Li, Xianjing;Bu, Wenhuan;Jin, Nianqiang;Meng, Yuan;Wang, Yi;Wang, Duan;Xu, Xiaowei;Zhou, Ding;Sun, Hongchen

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牙髓损伤是临床上最常见的疾病之一,严重者往往伴有牙齿功能的丧失,而目前临床上的治疗方式仅为洞型充填,没有牙本质-牙髓复合体的再生,从而导致牙齿失活和脆断。本研究以抗坏血酸和聚乙烯亚胺为原料,采用水热法制备了具有良好生物相容性的碳量子点。所制备的CDots能够增强人牙髓干细胞(DPSC)分泌细胞外基质(ECM),从而增加细胞在ECM上的粘附,增强DPSC的成骨/成牙分化能力。通过转录组分析、Western blot分析和分子动力学模拟揭示了CDots增强ECM分泌的机制,证实CDots的药理学活性来源于自噬的合理激活,自噬是通过调节磷酸肌醇3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶点信号通路介导的。基于CDots诱导的丰富ECM,从而增强细胞-ECM粘附,可以获得完整的牙髓干细胞片,这反过来促进牙本质-牙髓复合体以及血管的有效再生。
Pulp injury is one of the most common clinical diseases, and severe cases are usually associated with the functional loss of the tooth, while the current clinical treatment modality is only a cavity filling procedure without the regeneration of the dentin-pulp complex, thus leading to a devitalized and brittle tooth. In this study, carbon dots (CDots) with excellent biocompatibility are prepared from ascorbic acid and polyethyleneimine via a hydrothermal method. The as-prepared CDots can enhance extracellular matrix (ECM) secretion of human dental pulp stem cells (DPSCs), giving rise to increased cell adhesion on ECM and a stronger osteogenic/odontogenic differentiation capacity of DPSCs. Further, the mechanism underlying CDots-enhanced ECM secretion is revealed by the transcriptome analysis, Western blot assay and molecular dynamics simulation, identifying that the pharmacological activities of CDots are originated from a reasonable activation of the autophagy, which is mediated by regulating phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway. Based on the abundant CDots-induced ECM and thereby the reinforcement of the cell-ECM adhesion, an intact dental pulp stem cell sheet can be achieved, which in return promote in vivo the efficient regeneration of dentin-pulp complex as well as blood vessels.
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