正畸牙移动过程中，牙周组织免疫微环境的变化是力学刺激影响牙槽骨重塑的重要中间步骤，然而相关的力学-生物化学信号转导机制却鲜见报道。结合以往研究和申请人前期研究结果，我们认为正畸力加载下牙周膜细胞释放IL-33，有可能通过诱导osteomacs的表型改变和分泌功能产生信号级联，进而调控牙槽骨重塑。为验证该假说，本课题以“应力加载-IL-33–osteomacs–牙槽骨重塑”为主线，采用基因修饰 、抗体阻断、化学拮抗等方法对科学假说中的关键因子进行增效或失效，逐层深入研究应力加载下osteomacs介导的IL-33 影响牙周组织免疫微环境、进而调控牙槽骨重塑的分子机制。该研究将从骨免疫学的角度揭示牙周组织中的力学-生物化学信号转导机理，为认识牙移动的生物学过程、有效控制牙移动开启新的思路；同时揭示osteomacs这一骨膜细胞新成员与骨骼细胞间的串话机制，为骨骼系统相关疾病的治疗提供潜在的靶点

During orthodontic tooth movement, the immune micro-system in the periodontal tissue mediates mechanical stress-induced alveolar bone modeling and remodeling, the molecular mechanism is unknown though. Based on literature review and our previous study, we hypothesize that mechanical stimuli triggered IL-33 release from periodontal ligament (PDL) cells, and induced osteomacs phenotypic changes and cytokine release, thus impacted on alveolar bone modeling and remodeling. To test this hypothesis, we plan to track the mechanical load - IL-33 – osteomacs - alveolar bone, through medication or genetic manipulation of the signaling cascades. This study is expected to uncover the mechanism of immune-regulatory signaling transduction under stress in the PDL, and to provide new perspectives for biological strategies aiming at effectively controlling orthodontic tooth movement, and for providing potential therapeutic targets for treatment of various kinds of bone diseases.