牙槽骨是口腔功能的基础，我们已证实牙槽骨会发生骨质疏松，防止骨质疏松牙槽骨骨量丢失的学科意义重大。前期建立咬合应力丧失模型，发现咬合应力通过促进成骨改建在防止骨丢失中发挥关键作用。牙槽骨是如何感受咬合应力并转化为生物信号，机制不明。机械敏感钙离子通道蛋白Piezo1是最新解析的力敏感离子通道蛋白，课题组前期选用Prx1-Cre构建BMSCs特异Piezo1敲除小鼠，发现其可促进成骨改建且对应力敏感。经过初步验证，提出假设：咬合应力可能通过激活Piezo1促进BMSCs成骨向分化，从而在增强成骨改建防止骨质疏松牙槽骨骨丢失中发挥重要作用。本项目拟在前期基础上，构建诱导型条件敲除模型，利用免疫共沉淀、激活或阻断下游通路等技术，并进行体内验证，系统研究Piezo1在咬合应力调控牙槽骨成骨改建中的机制，既为力学调控骨质疏松牙槽骨改建机理提出新认识，又为发现新靶点防止骨丢失，开拓新的力学生物学思路。

Alveolar bone is the foundation of oral function. Our previous study confirmed that estrogen deficiency could induce alveolar bone loss and osteoporosis. Prevention of alveolar bone loss under osteoporosis is critical for oral function and treatment. With an occlusal stress loss model， we found occlusal stress play an important role in prevention of alveolar bone loss via promoting bone formation remodeling in OVX rats. However, it is still unclear that the mechanism by which alveolar bone feels and transducts the occlusal stress. Piezo1 is a type of mechanosensitive ion channel protein whose protein structure has been described in 2018. With a bone mesenchymal stem cells (BMSCs) specific Piezo1 knockout mice model with prx1-Cre, we found Piezo1 can promote bone formation remodeling and is quite sensitive to the stress. We hypothesized that the occlusal stress may promote the osteogenic differentiation of BMSCs by activating Piezo1, thus playing an important part in enhancing the bone remodeling to prevent bone alveolar loss under osteoporosis. Based on the previous experiments, this project intend to construct conditional knockout animal model, utilize the technique of immune coprecipitation and activating or blocking downstream pathway, verify in vivo, to systematically explore the role of Piezo1 in occlusal stress-induced alveolar bone formation remodeling. It will not only be helpful to obtain a new understanding of biomechanical regulation of osteoporotic alveolar bone remodeling, but also meaningful to find a new target to prevent bone loss and develop fresh insights of mechanical biology.