压应力环境下FoxO3/SOD3环路介导巨噬细胞极化失衡导致炎性牙根吸收的研究

牙根吸收是正畸常见并发症，机制不明。牙骨质/成牙骨质细胞是抵抗牙根吸收的屏障，SOD3作为特异性高表达标志物可能是抗吸收特性来源。课题组前期研究发现压应力环境下牙骨质吸收的发生与炎症反应密切相关，FoxO3/SOD3反馈环路参与调控，推论压应力环境下，FoxO3/SOD3反馈环路由负到正转化，并介导巨噬细胞极化失衡，从而打破牙骨质稳态，引发炎症瀑布，触发牙根吸收。本项目结合体内、体外实验和组学分析等手段，通过系统性建立应力炎症模型验证“应力-炎症-牙根吸收”关系；通过过表达或沉默FoxO3、SOD3，探究FoxO3/SOD3反馈环路的转化规律及调控；并进一步通过调控巨噬细胞极化失衡，探究对应力环境下炎症反应及牙根吸收的影响，层层递进验证“应力-FoxO3/SOD3反馈环路-巨噬细胞极化-炎症-牙骨质吸收”应答通路，为阐明“正畸导致的炎性牙根吸收”发生机制提供新思路，为该疾病防治提供新策略。

Orthodontically induced inflammatory root resorption is the most common complication in orthodontic treatment, without clear mechanism and lack of effective therapy. Cementum and cementoblast are the main defense against root resorption. SOD3, as identified exclusively strong expressed in cementum, may contribute to the property against root resorption. We previously found that cementum resorption went together with inflammation under mechanical stress, which had a regulation loop between FoxO3 and SOD3. So we hypothesize that in the inflammatory-dependent cementum resorption under compressive force, FoxO3/SOD3 loop changes from negative feedback to positive feedback, which inducing macrophage polarization imbalance., following with the cementum homeostasis transforms to resorption with inflammatory cascade. To verify the hypothesis, we intend to use multiple animal models, cell models and multi-omics analysis to verify the “force-inflammation-cementum resorption”relationship, confirm the inflammatory-dependent cementum resorption model, explore the FoxO3/SOD3 loop variation and regulation, as well as the following induced macrophage polarization. The results can reveal the “force-FoxO3/SOD3 loop-macrophage polarization-inflammation-cementum resorption” way step by step, which may provide new strategies for treatment for this disease.