牙周膜细胞通过外泌体miRNA-9-5p调控巨噬细胞炎症反应介导力刺激下牙槽骨吸收的机制研究

研究显示机械力刺激能够诱发无菌性的牙周组织炎症反应并导致牙槽骨吸收。申请者前期研究发现牙周膜细胞（PDLCs）能感知牵张刺激，通过激活炎症体引发炎症反应，但PDLCs如何介导力相关牙周炎症中牙槽骨吸收尚不清楚。巨噬细胞在促进破骨细胞分化、炎性骨吸收中扮演了重要角色，但力诱导产生的炎症信号如何由PDLCs传递至巨噬细胞不得而知。外泌体介导的细胞间信号传递在炎症中的作用逐渐显露，申请者也证实牵张诱导PDLCs分泌外泌体，其中miRNA-9-5p高表达，而有报道miRNA-9-5p可能调控巨噬细胞炎症反应。因此，本课题提出PDLCs在牵张刺激下能够通过外泌体携带miRNA-9-5p定向调控巨噬细胞极化状态、介导力刺激牙周炎症反应和牙槽骨吸收的科学假说，拟通过细胞实验和动物实验予以证实，并探索其分子机制，对于进一步揭示力相关牙周炎症疾病的发生发展机制，以及寻找可能的治疗靶点具有重要的科学意义。

Studies have shown that mechanical forces can induce sterile inflammation in periodontal tissue and lead to alveolar bone resorption. Our previous research showed that periodontal ligament cells (PDLCs) can sense stretch stimuli and trigger inflammatory responses by activating inflammasomes, but how PDLCs mediate alveolar bone resorption in force-related periodontal inflammation remains unclear. Macrophages play an important role in promoting osteoclast differentiation and inflammatory bone resorption, but the transduction pathway of the force-induced inflammatory signals between PDLCs and macrophages is unknown. The role of exosomes-mediated intercellular signaling in inflammation has been discovered recently. We have also confirmed that stretch induced PDLCs to secrete exosomes containing miRNAs, of which miRNA-9-5p was highly expressed. Considering recent reports indicating that miRNA-9-5p may be involved in macrophage inflammatory responses, we here propose a hypothesis that PDLCs can mediate force-induced periodontal inflammation and alveolar bone resorption by regulating the polarization states of macrophages through exosomes carrying miRNA-9-5p in response to stretch stimulation. Cell experiments and animal experiments will be carried out to verify the hypothesis and explore the molecular mechanisms in this process. Our research will be of scientific value for further revealing the mechanisms of the initiation and progress of force-related periodontal inflammatory diseases and seeking for possible therapeutic targets.