PIEZO1介导感觉神经纤维调控牙槽骨重塑的机制

力学刺激下牙周组织发生信号转导、组织改建是正畸牙移动的基础，然而牙周组织感应、转导力学信号进而影响骨改建的机制尚不明确。本课题前期研究表明，应力加载下，机械门控离子通道PIEZO1在牙周膜中的时空分布与神经肽CGRP基本一致、与YAP表达呈正相关，并与牙槽骨改建活跃程度紧密相关。由此提出，正畸力触发牙周膜内感觉神经纤维的PIEZO1离子通道，激活PIEZO1-YAP信号调控神经肽释放，影响局部免疫微环境，并与骨骼细胞、抗原呈递细胞产生信号串话，从而调控牙槽骨重塑。为验证该假说，本研究以感觉神经特异性基因敲除小鼠和牙移动模型为研究载体，通过对PIEZO1-YAP-CGRP/SP信号轴中各级分子进行基因修饰或抑制，逐层深入揭示应力下PIEZO1介导感觉神经纤维转导力学信号、调控牙槽骨重塑的机制。该研究将从神经科学的角度为阐释正畸牙移动的生物学过程开辟新视野，为实现安全、高效的牙移动提供新思路。

Stress-induced signal transmissions and tissue reconstructions of teeth-alveolar bone complex are the biological foundation of orthodontic tooth movement. However, how does periodontal tissue receive, transmit and transform stress signals and modulate bone modeling remains unclear. Our previous studies found that, the dynamic of bone modeling and bone remodeling are related to the spatio-temporal distribution of sensory nerve fiber markers and activity of mechanical gated ion channel PIEZO1 in the periodontal ligaments. Based on these preliminary studies, we hypothesize that the application of orthodontic stress triggers the PIEZO1 of sensory nerve fibers in periodontal ligaments. Activation of PIEZO1-YAP signal axis induces reconstructions of cytoskeleton and releases of neuropeptitde CGRP/SP, which changes the immune microenvironment and crosstalk between skeletal cells and antigen presenting cells to further modulate bone modeling. To verify this hypothesis, conditional transgene mouse and orthodontic tooth movement model would be applied to explore the novel mechanisim that PIEZO1 on sensory nerve fiber induced biochemechanical transformation and bone modeling under mechanical stress. This study would illustrates the mechanism of orthodontic tooth movement in a novel perspective of neuroscience, and provides new insights into promotion of periodontal tissue remodeling and therapy of controllable and accelarated orthodontic tooth movement.