EndMT在正畸牙周改建中的作用及机制研究

口腔正畸治疗的实质是矫治力作用下的牙周组织改建。MSCs在牙周组织改建中的作用现已证实。课题组前期研究发现正畸牙移动牙周组织内MSCs数量明显上调且集中在血管周围。但新生MSCs来源目前尚不清楚。2010年Nat Med首次报道血管内皮细胞通过EndMT转化形成MSCs样细胞，并证实EndMT并非仅局限在胚胎发育阶段或组织纤维化的病理过程，生理状态下亦可发生。2011年Cell stem cell评述认为体内血管内皮细胞相当于MSCs的储存库。我们推测正畸牙周组织内MSCs新生与血管密切关系，EndMT是正畸牙周组织MSCs新生、牙周组织改建的重要机制。因此，本项目拟应用正畸牙移动模型，观察牙周组织改建中的EndMT发生；并通过应力培养体系，探讨应力刺激对EndMT的影响及以ALK2为核心的信号通路。该项目将为完善正畸牙周改建理论及构建基于EndMT机制的正畸牙移动临床干预路径提供依据。

The essence of orthodontic treatment is periodontal tissue remodeling under orthodontic force. The function of mesenchymal stem cells (MSCs) in periodontal remodeling has been confirmed. The pilot studies of our research group found that the number of multipotent stem-like cells in periodontal ligament increased significantly after orthodontic loading, which distributed mainly in perivascular area. However, the origin of these newly generated MSCs is not clear. In 2010, Nat Med reported vascular endothelial cells could convert into multipotent stem-like cells by the mechanism of endothelial-to-mesenchymal transition (EndMT); besides, this process was not just confined to the stages of embryonic development or pathological fibrosis, but also occurs under physiological states. In 2011, Cell Stem Cell suggested that the perivascular endothelial cells could be the in vivo counterparts of cultured MSCs. Based on these previous studies, we speculate that the newly emerged multipotent stem-like cells in periodontal ligament might have a substantial connection with vascular endothelial cells, and EndMT might be the mechanism that regulate the periodontal remodeling. Therefore, our project aims to observe the occurance of EndMT in periodontal remodeling by establishing animal models of orthodontic tooth movement. Moreover, we plan to establish the cultural system under stress stimuli, aiming to explore the effect of mechanical stimuli on EndMT and relevant pathway centered on ALK2. This project would not only lay solid foundation to optimize the theory of orthodontic periodontal remodeling, but also establish the approach based on EndMT to intervene the teeth movement in vivo.