牙周膜干细胞源性外泌体对正畸矫治力所致牙根吸收的修复过程的调控机理研究

Orthodontically induced root resorption is an unavoidable adverse reaction in clinical treatment. Therefore, how to prevent orthodontic root resorption and promote the repair of orthodontically induced root resorption has always been the primary concern for orthodontics. Periodontal ligament stem cell exosome (PDLSC-Exo), as a communicator of intercellular functional bioactive substances, may participate in the repair process of root resorption induced by orthodontic treatment, and may be achieved by affecting the biological activity of cementoblasts. The objective of this study is to investigate: 1) the effects of PDLSC-Exo on the repair process of root resorption induced by orthodontic treatment were explored through PDLSC-Exo or microRNA-21 given at different concentrations respectively in vivo and in vitro. 2) PDLSC-Exo/microRNA-21 regulated the apoptosis, differentiation and functional activity of cementoblasts; 3) Molecular mechanisms related to the effects of PDLSC-Exo/microRNA-21 on PI3K/Akt and Wnt/beta-catenin pathways. The results will reveal the regulation mechanism of PDLSC-Exo/microRNA-21 in the repair process of orthodontically induced root resorption, and provide new ideas for preventing root resorption induced by orthodontic treatment and promoting root resorption.

正畸牙根吸收是临床治疗中不可避免的不良反应，如何促进牙根吸收的修复一直是研究的热点。牙周膜干细胞源性外泌体（PDLSC-Exo）作为胞间功能性生物活性物质的通讯者，可能参与调控了正畸矫治力所致牙根吸收的修复过程，并可能是通过影响成牙骨质细胞生物活性来实现的。本课题拟通过体内正畸牙根吸收动物模型和体外成牙骨质细胞培养，分别给予不同浓度PDLSC-Exo或miRNA-21抑制剂，探索1）PDLSC-Exo在正畸矫治力所致牙根吸收的修复过程中发挥的作用；2）PDLSC-Exo/miRNA-21对成牙骨质细胞的增殖、分化及功能活性的调控作用，及其PI3K/Akt和Wnt/β-catenin信号通路相关分子机制。研究结果将揭示PDLSC-Exo/miRNA-21对正畸矫治力所致牙根吸收的修复过程的调控机理，为预防正畸所致牙根吸收的发生和促进牙根吸收的修复提供新的思路。

在正畸临床矫治过程中，牙齿会发生不同程度的牙根吸收，如何预防正畸牙根吸收，促进牙根吸收的修复一直是正畸医生们关注的焦点问题。干细胞源性外泌体（Exosomes）是不同组织间、细胞间信号交流的重要介导物质，通过与目标组织或细胞相互识别，释放其内含的生物活性物质，促进靶部位的细胞增殖、迁移、分化，在骨重建、骨损伤修复中发挥重要作用。本研究选择牙周膜干细胞源性外泌体，观察其对牙槽骨损伤及牙根吸收的修复过程的影响；不同浓度干细胞外泌体对靶细胞凋亡、迁移及矿化的作用；探索外泌体调控成骨及成牙骨质细胞功能活性的胞内信号通路。研究发现：干细胞源性外泌体能够促进牙槽骨缺损及牙根吸收的修复过程；牙周膜干细胞外泌体促进成牙骨质细胞增殖、迁移及矿化；不同浓度外泌体影响成牙骨质相关矿化因子基因及蛋白量的表达，其中50μg/ml外泌体刺激后矿化因子表达量增高最明显；干细胞源性外泌体能够激活成骨及成牙骨质信号通路，并通过PI3K/Akt/YAP信号通路调控成骨及成牙骨质矿化相关因子的表达。本课题对进一步探讨外泌体促成骨、成牙骨质的效果有重要意义，为促进牙根修复及牙周组织再生的作用机制奠定了理论基础。