靶向调控周细胞PDGFR-β信号通路对拔牙正畸牙槽骨-血管重塑的影响及机制研究

优化正畸拔牙区牙槽骨改建相对平衡以避免牙移动障碍与相应牙周风险是正畸临床亟待解决的重要问题。明确拔牙创骨改建调控机制及关键效应细胞是解决该问题的重点。2014年Nature首次报道H型血管能够正向调控成骨活动，揭示了血管-成骨偶联的重要机制。周细胞具有促进血管新生及直接分化成骨的双重功能，其是否为调控H型血管-成骨偶联的关键靶点尚属未知。课题组前期研究发现周细胞与H型血管分布具有相似性，周细胞及其介导的PDGFR-β信号通路在拔牙创成骨过程中具有重要作用。基于研究现状与前期基础，本项目拟建立周细胞基因报告及示踪小鼠培养体系，运用最新组织透明化三维成像技术及基因编辑技术，深入探讨周细胞参与牙槽窝骨-血管重塑的生物学活动及PDGFR-β靶向调控机制。该项目的顺利实施将有望通过靶向激活周细胞PDGFR-β优化拔牙区骨改建平衡及骨组织条件，为高效安全的正畸牙移动奠定实验基础。

It is critical and urgent to optimize alveolar bone remodeling in avoid of tooth-movement trouble and corresponding periodontal risks. Probing the key cells and regulatory mechanics under bone remodeling in tooth-extraction site is of importance. It was firstly reported by Nature in 2014 that H-type blood vessel can positively mediate osteogenesis, suggesting angiogenesis-osteogenesis coupling to be a crucial mechanism under bone formation. Pericytes play a role in both angiogenesis and osteogenic differentiation, yet its function in angiogenesis-osteogenesis coupling is far from clarity. Our group has detected the similar distributional pattern of pericytes to H-type blood vessel, and further, the vital role of PDGFR-β signaling mediated by pericytes in osteogenesis at extraction site. On the base of recent research progress and our findings, we plan to apply latest PEGASOS-based 3D imaging and CRISPR-Cas9 gene editing technology to explore the biological function of pericytes in bone-vessel remodeling and the regulatory role of PDGFR-β. This project will lay the foundation for PDGFRβ-pericyte-targeted therapy for alveolar bone atrophy, which paves a way for effective and safe orthodontics.