TNF-α/NF-κB信号通路在正畸牙移动中PDLSCs介导的炎症调控中的作用及机制研究

正畸炎性牙根吸收（OIIRR）是牙颌畸形矫治中亟待解决的常见并发症。OIIRR及正畸牙移动均是正畸力启动下的骨免疫过程，破骨活动亢进是OIIRR发生的重要原因。牙周膜间充质干细胞（PDLSCs）因其特异的牙周膜分布和对免疫炎症有效的调控能力而倍受关注。申请者前期研究结果提示，PDLSCs的免疫调节能力与牙周局部炎性水平二者之间的失衡可能是OIIRR的重要发生机制。结合最新揭示的TNF-α/NF-κB信号通路在骨免疫及MSCs免疫调节中的重要作用，本项目拟应用正畸牙移动模型完善牙周组织中的炎症因子谱；验证PDLSCs对正畸牙移动牙周局部炎症水平的调控作用；进一步探讨应力刺激下TNF-α/NF-κB信号通路对PDLSCs免疫调节功能的影响机制。该项目为阐明以PDLSCs免疫调节能力与炎症水平平衡为基础的正畸牙移动牙周改建机制及构建基于PDLSCs免疫调节机制的OIIRR的临床干预路径提供依据。

Orthodontically induced inflammatory root resorption (OIIRR) is a common and serious consequence of orthodontic tooth movement. OIIRR and orthodontic tooth movement are both osteoimmunologic processes evoked by orthodontic force. In recent years, the immunomodulatory and anti-inflammatory properties of periodontal ligament-derived MSCs(PDLSCs)have been emphasized. Base on the previous researches and the pilot studies of our research group, we speculate that the PDLSCs modulate the local aseptic inflammation of the orthodontic tooth movement, and the imbalance between them might be the pathogenesis of OIIRR. Combining the newly discovered role of TNF-α/NF-κB signaling during osteoimmunologic process and immunomodulation of PDLSCs, our project design is as follow: complete the spectrum of inflammatory cytokines in the periodontal tissue during orthodontic tooth movement; verify the anti-inflammatory properties of PDLSCs in the orthodontic process; explore the mechanism of TNF-α/NF-κB signaling effecting on immunomodulatory properties of PDLSCs. This project would clarify the mechanism of periodontal tissue remodeling based on the balance of the immunomodulatory properties of PDLSCs and the level of inflammation, as well as establish the effective approach to intervene the OIIRR.