正畸牙移动过程中，牙周膜细胞作为牙周组织对力学刺激的感知器和效应器，会发生表型和功能的改变，此过程是力学信号得以传递和整合的关键步骤。结合已有研究线索和前期研究结果，我们认为力学刺激作用下牙周膜细胞向肌成纤维细胞的分化，很可能是由转录激活因子YAP/TAZ介导的力学-化学信号转导和整合，并通过RhoA/ROCK-F-actin-YAP/TAZ-TEAD信号通路实现的。为验证该假说，本研究以YAP/TAZ核浆穿梭为切入点，联合体内体外实验通过改变YAP/TAZ的表达，结合干扰RhoA/ROCK-F-actin-YAP/TAZ-TEAD信号通路上各不同位点，探索YAP/TAZ调控牙周膜肌成纤维细胞分化的分子机制。该研究将深入揭示力学信号在牙周膜中的传递过程，为正畸临床提高牙周组织改建水平、有效控制牙移动提供新的思路；同时为肌成纤维细胞相关疾病的治疗提供潜在的生物学靶点。

Periodontal ligament cells (PDLCs), as the senor and effecter of mechanical stimuli, change the phenotype and function during orthodontic tooth movement. This process is the key to mechanical signal transduction and integration. Considering the literature reviews and our previous research, we made a conclusion that differentiation from PDLCs to myofibrobalsts (MFB) under the mechanical stimulation might be regulated by RhoA/ROCK-F-actin-YAP/TAZ-TEAD signal pathway, in which YAP/TAZ played the central role. To test this hypothesis, we plan to trace the nucleocytoplasmic shuttling of YAP/TAZ. The YAP/TAZ-mediated PDLCs-myofibroblast transition under mechanical loading will be explored both in vivo and in vitro, through genetic manipulation of YAP/TAZ. Furthermore, the molecular mechanism of PDLCs-myofibroblast transition will be examined in detail in vitro, by medication or genetic manipulation of the signaling cascades in this signal pathway. This study is expected to uncover the mechanism of mechanotransduction in the periodontal ligament (PDL), and to provide new insights into biological strategies aiming at promoting the periodontal tissue remodeling and effectively controlling orthodontic tooth movement. This study also holds special hope for providing potential therapeutic targets for treatment of various kinds of myofibroblast-related diseases.