机械感应蛋白Piezo1在Gli1+MSCs介导的牙槽骨重建中作用的透明化观察及机制探究

优化拔牙区骨重建、避免骨量不足造成的牙移动障碍及牙周风险是口腔正畸和种植临床亟待解决的问题之一。间充质干细胞(MSCs)可作为牙槽骨重建的关键细胞来源和调控靶点；咬合应力是影响牙槽骨愈合微环境的重要因素。近日，申请人及合作者于Nature长文揭示了Piezo1在应力调控长骨祖细胞成骨中的关键地位，但其是否参与应力刺激下MSCs介导的牙槽骨重建过程目前尚属未知。申请人前期研究发现，Gli1+MSCs是牙槽骨重建的重要细胞来源，且具有应力敏感性；Piezo1受咬合力调控，参与维持Gli1+细胞活性及骨改建水平。基于此，本项目拟结合特异性基因敲除小鼠及课题组最新研发的组织透明化技术，从三维水平揭示Piezo1响应力学信号对Gli1+细胞参与的牙槽骨重建的调控作用及生理机制，探讨其激活对位点保存的可能效果。研究结果有望通过对MSCs的靶向调控优化牙槽骨重建，为高效安全的正畸和种植治疗奠定理论基础。

To optimize alveolar bone modeling in avoid of tooth-movement trouble, osseointegration failure and corresponding periodontal risks is a critical and urgent topic in dental clinics. Mesenchymal stem cells (MSCs) could serve as a main cell source and regulating target for alveolar bone healing. Occlusal hypofunction upon tooth extraction would disturb the micro-environment of bone healing. In 2021, an article by the applicant and collaborators published in Nature revealed the key role of Piezo1 in regulating mechanical force and osteogenic progenitors. However, it is still unknown whether this protein plays its part in regulating Gli1+ MSC-mediated socket healing. Previous studies by the applicant suggested that Gli1+ cells within alveolar bone marrow are main contributors to tooth extraction socket healing, which is regulated by occlusal force. Expression level of Piezo1 is correlated with mechanical force, and its activity affects the activation of Gli1+ cells and related bone formation. In this project, we will utilize the latest tissue clearing and 3-dimensional imaging technique to get better understanding of Piezo1 in Gli1+ cells. We aim to reveal its role in force-mediated alveolar bone healing and the mechanisms within. Further we aim to test whether the upregulation of Piezo1 would promote extraction socket preservation. This project will lay the foundation for cell-based therapy for alveolar bone atrophy, which paves a way for safe orthodontic and implantology treatment.