IKK-NF-κB与Wnt/β-catenin信号通路在咬合创伤调控根尖周骨代谢中的作用机制

Occlusal trauma is a common and frequently-occurring disease which dose harm to the health of human being. One of the symptoms is alveolar bone resorption. In normal conditions, bone formation and resorption is in a state of dynamic balance, and the balance may be broken by occlusal trauma, then alveolar bone resorption will be happened. In our previous study, we found that inflammation influences alveolar bone metabolism. Research has shown that IKK-NF-κB signaling pathway is closely related to inflammation, and plays a critical role during bone metabolism together with Wnt/β-catenin signaling pathway. However, it remains to be researched that the mechanism and cross talk between the two signaling pathway during traumatic force influencing bone metabolism. Our project will take the MC3T3-E1 cell and RAW264.7 cell with traumatic force loading and the rat model of occlusal trauma as in vitro and in vivo research objects respectively. The mechanism of the IKK-NF-κB and Wnt/β-catenin signaling pathway in traumatic force influencing bone metabolism will be investigated systematically. Our project will enrich the research of occlusal trauma in molecular biology level, and provide the theory basis for preventing the happening of the periodontal and periapical diseases and regulation of alveolar bone metabolic balance.

咬合创伤是口腔常见病多发病，严重危害人体健康，其主要表现为牙槽骨破坏吸收。正常情况下骨形成与骨吸收处于动态平衡状态，而在所受应力过大形成咬合创伤的情况下会被打破，导致牙槽骨吸收。我们前期研究发现炎症可影响根尖周骨代谢。国内外研究表明IKK-NF-κB通路的激活与炎症密切相关，且与Wnt/β-catenin通路在骨代谢中共同发挥重要作用。然而这两种信号通路间的串话作用机制以及创伤咬合力对其影响未见报道。本项目将以咬合创伤力加载的成骨及破骨细胞株（MC3T3-E1和RAW264.7）为体外研究对象，以大鼠咬合创伤模型为在体研究对象，系统探讨咬合创伤力作用下IKK-NF-κB与Wnt/β-catenin信号通路在根尖周骨代谢中的作用机制。本项目将充实咬合创伤分子生物学层面的研究，为预防牙周和根尖周疾病的发生和调控牙槽骨代谢平衡提供理论依据。

咬合创伤是口腔常见病、多发病，严重危害人体健康，其表现之一为牙槽骨吸收。正常情况下骨形成与骨吸收处于动态平衡状态，而在所受应力过大形成咬合创伤的情况下会打破平衡，导致牙槽骨吸收。我们的前期研究发现炎症可影响根尖周骨代谢，国内外研究表明IKK-NF-κB通路的激活与炎症密切相关，且与Wnt/β-catenin通路在骨代谢中共同发挥重要作用。然而这两种信号通路间的串话作用机制以及创伤咬合力对其影响未见报道。.本项目以咬合创伤力加载的成骨细胞株（MC3T3-E1）为体外研究对象，以大鼠咬合创伤模型为在体研究对象，系统探讨咬合创伤力作用下IKK-NF-κB与Wnt/β-catenin信号通路在根尖周骨代谢中的作用机制。研究发现机械压应力通过IKK-NF-κB信号通路抑制MC3T3-E1细胞的成骨分化与Wnt/β-catenin信号通路有关。阻断IKK-NF-κB信号通路后，MC3T3E1细胞成骨分化增加。体内实验证实咬合创伤通过激活IKK-NF-κB信号通路抑制成骨。此外，机械压应力能通过下调非经典Wnt信号Wnt4的表达来抑制成骨。本项目结果充实了咬合创伤分子生物学层面的研究，为预防牙周和根尖周疾病的发生和调控牙槽骨代谢平衡提供理论依据。