IL-17F通过C/EBPβ调控免疫抑制状态下骨改建及种植体骨结合的研究

种植义齿是目前最佳的缺牙修复方式。随着免疫抑制人群快速扩增，该人群缺牙后的种植需求增加。免疫抑制影响骨改建和骨愈合。申请人前期发现，免疫抑制导致种植体骨结合下降，骨缺损修复延迟，同时伴体内IL-17F降低；进一步研究显示，IL-17F促进正常小鼠的骨折愈合，提示免疫抑制可能通过IL-17F影响骨结合和缺损修复。IL-17F介导C/EBPβ表达，后者协同Runx2调节成骨。基于此，本项目拟建立免疫抑制小鼠模型，并给予外源性IL-17F，研究IL-17F在免疫抑制小鼠骨改建和种植体骨结合中的治疗效果；进一步探究IL-17F的下游靶点，明确IL-17F是否通过调节C/EBPβ的表达发挥功能，并利用CRISPR/Cas9敲除C/EBPβ，进行负向验证。研究结果将阐明免疫抑制调控种植体骨结合的机制，探索免疫抑制条件下促进种植体骨结合的治疗靶点，为提高免疫抑制人群的种植修复效果提供实验基础。

At present, dental implant is the most reliable approach for the restoration of missing teeth. With the number of immunocompromised persons rapidly increasing, the demand of dental implant for restoring lost teeth in immunosuppressive population accordingly increases. It is reported that immunosuppression impairs bone remodeling and healing. Our research team found that immunosuppression leads to reduction on the osseointegration of titanium implant and delay of bone defect healing, along with the reduction of cytokine IL-17F expression. Further study revealed that IL-17F is benefit for bone healing of fracture in normal mice. Previous study showed that IL-17F modulates the expression of C/EBPβ, which can regulate osteogenesis by synergistic action with transcription factor Runx2. In this research project, immunosuppressive mouse model will be established. Then, exogenous IL-17F will be administered to immunosuppressed mice to study the effect of IL-17F on bone remodeling and implant osseointegraion. Furthermore, we plan to explore whether IL-17F influence osteogenesis via C/EBPβ in immunosuppressive condition using CRISPR/Cas9. The results will clarify the regulatory mechanism of implant osseointegration and explore the treatment target to enhance osseointegration under immunosuppressive circumstance, thus providing theoretical guidance and experimental basis for improving the outcome of dental implant in immunosuppressive patients.