机械力作用下牙周膜干细胞介导的免疫调节参与正畸牙齿移动的机制研究

Mechanical force-induced orthodontic tooth movement (OTM) is associated with inflammatory bone remodeling. We recently found out that immune system involved in alveolar bone remodeling and the consequent OTM. Force-regulated activation of macrophages and T lymphocytes play an important role in OTM. In addition, mesenchymal stem cells (MSC) could interact with immune cells. the immuno-microenvironment play an important role in MSC modulated bone remodeling. Periodontal ligament mesenchymal stem cells (PDLSCs), as one of the most important cells in periodontal ligament, could be activated by mechanical force and interact with other cells. However, whether and how PDLSCs involved in OTM under mechanical force are still unclear.. In this project, we try to explore whether force-regulated immunomodulation of PDLSCs involves in orthodontic tooth movement. We try to detect local changes of PDLSCs, immune cells and osteoclasts in OTM animal models, and detect the changes of immunomodulation of PDLSCs after mechanical force application. This study on the one hand helps us understand the molecular mechanisms of orthodontic tooth movement, and on the other hand provides us a new way to explore the influence of mechanical force on bone remodeling.

正畸牙齿移动（orthodontic tooth movement, OTM）是机械力引起牙周组织反应及牙槽骨改建使牙齿在牙槽骨中移动的过程。本课题组近期研究表明免疫系统参与OTM，加力后牙周组织中的巨噬细胞、T细胞等免疫细胞在OTM及牙槽骨改建中发挥重要作用。间充质干细胞具有免疫调节功能，局部免疫微环境在干细胞介导的骨改建中至关重要。牙周膜干细胞作为牙周组织中的间充质干细胞，能够感受机械力。然而，机械力能否影响牙周膜干细胞的免疫调节作用，从而参与OTM及骨代谢尚不明确。本项目拟在前期研究的基础上，利用OTM动物模型及体外干细胞加力模型探讨机械力如何影响牙周膜干细胞的免疫调节作用，从而参与OTM与骨改建。本项目一方面有助于理解正畸牙齿移动分子生物学机制，探索加速正畸牙齿移动的新方法；另一方面也为理解力学刺激对骨改建过程的影响提供了新的思路。

力学刺激在决定干细胞的行为，引导组织发育，维持组织稳态等方面起着重要作用。然而，机械力刺激是否及如何调节间充质干细胞的功能，从而参与骨改建过程仍尚不清楚。间充质干细胞具有免疫调节作用，然而，在机械力作用下干细胞是否及如何调节免疫细胞的功能，从而影响骨改建仍需进一步探讨。正畸牙齿移动是机械力引起牙周组织反应及牙槽骨改建使牙齿在牙槽骨中移动的过程。牙周膜干细胞（periodontal ligament stem cells, PDLSCs）作为牙周组织中的间充质干细胞，能够感受机械力并影响周围细胞的功能。本项目利用牙齿移动动物模型及体外干细胞静压力刺激模型，探讨机械力如何影响PDLSCs的免疫调节作用，从而参与牙齿移动与骨改建。.研究结果显示机械力刺激通过激活PDLSCs中钙离子通道（TRP subfamily V member 4，TRPV4）的表达，调节PDLSCs的增殖，分化及免疫调节能力，从而参与骨改建及牙齿移动过程。此外，机械力刺激下PDLSCs释放的重要气体分子H2S通过STAT1信号通路促进炎症性M1型巨噬细胞的极化，从而影响骨改建及牙齿移动。本项目一方面有助于理解正畸牙齿移动分子生物学机制，探索加速正畸牙齿移动的新方法；另一方面也为理解力学刺激对骨改建过程的影响提供了新的思路。