牙周膜干细胞来源外泌体经Fas/FasL通路调控CD4+T细胞抑制正畸后复发机制的研究

干细胞外泌体调控骨改建和免疫稳态是影响局部牙槽骨成骨与破骨平衡的关键科学问题，但具体机制尚不明确。申请人前期研究证实，正畸过程中骨改建及后期稳定性的维持与局部牙周免疫稳态维持有关，阿司匹林给药可以调控牙周免疫稳态，发挥骨免疫调控作用并降低牙周微环境中TNF-α和IFN-γ表达水平，在骨重建的过程中抑制CD4+淋巴细胞和Th1细胞的产生并减少破骨细胞的数量。有助于降低复发风险，维持牙槽骨稳定。预实验和文献调研发现牙周膜干细胞来源外泌体可参与骨免疫及代谢调控，通过Fas/FasL信号通路抑制CD4+T细胞活性，诱导免疫细胞发生凋亡。为此，申请人拟构建相应细胞、动物加力模型，通过分子生物学、Micro-CT、组织工程等技术，以明确外泌体调控CD4+T细胞的机制，并探究外泌体通过Fas/FasL信号通路促进干细胞成骨的机制。项目研究成果为提高正畸牙移动效率和延缓复发提供了潜在临床应用价值。

The regulation of bone remodeling and immune homeostasis by stem cell exosomes is a key scientific issue affecting the balance between osteogenesis and osteoclastesis of local alveolar bone, but the specific mechanism is not clear. Previous studies of the applicant have confirmed that bone remodeling and the maintenance of late stability during orthodontic treatment are related to the maintenance of local periodontal immune homeostasis. Aspirin administration can regulate periodontal immune homeostasis, play a role in bone immune regulation, reduce the expression levels of TNF - α and IFN - γ in periodontal microenvironment, inhibit the production of CD4 + lymphocytes and Th1 cells during bone remodeling, and reduce the production of osteoclasts number. It is helpful to reduce the risk of recurrence and maintain the stability of alveolar bone. Pre experiment and literature research found that periodontal ligament stem cell-derived exosomes can participate in bone immune and metabolic regulation, inhibit the activity of CD4 + T cells through Fas / FasL signaling pathway, and induce apoptosis of immune cells. Therefore, the applicant intends to construct the corresponding cell and animal afterburner models, and clarify the mechanism of exosomes regulating CD4 + T cells through molecular biology, micro CT, tissue engineering and other technologies, and explore the mechanism of exosomes promoting stem cell osteogenesis through Fas / FasL signaling pathway. The research results of the project provide potential clinical application value for improving orthodontic tooth movement efficiency and delaying relapse.