NFAT5介导巨噬细胞极化在伴高血压牙周炎牙槽骨破坏中的作用及机制研究

伴高血压的牙周炎是口腔临床常见疾病。目前，伴高血压牙周炎患者的宿主反应和牙周组织破坏的分子机制尚不明确。文献报道巨噬细胞极化在牙周炎和高血压的发生发展中都具有重要作用；转录因子NFAT5能够靶向激活多种炎症相关基因，调控巨噬细胞极化和功能。申请人前期发现牙周炎小鼠的牙槽骨明显破坏并有大量高表达NFAT5的巨噬细胞浸润；体外牙龈卟啉单胞菌合并高盐环境中，巨噬细胞NFAT5表达水平明显升高并且主要定位在细胞核内；此外，NFAT5能够调控多条与细胞增殖、分化、炎症密切相关的信号通路。基于上述研究背景，我们提出伴高血压的牙周炎症微环境中，转录因子NFAT5介导巨噬细胞极化参与牙槽骨破坏的调控。为此本课题拟通过体内外实验，深入研究伴高血压的牙周炎症微环境中，NFAT5介导的巨噬细极化对牙槽骨破坏的影响，挖掘NFAT5下游靶基因以及相关调控网络。本项目有望为伴高血压的牙周炎患者的防治提供新思路。

Patients with periodontitis and hypertension are commonly observed in the dental clinic. The underlying mechanisms of the host response and periodontal tissue destruction remain unclear. Many studies suggest that macrophage polarization plays essential roles in the development of periodontitis and hypertension. The transcription factor NFAT5 can target and activate a variety of inflammation-related genes and regulate macrophage polarization and function. In our previous study, we found that increased infiltration of macrophages expressing high levels of NFAT5 was associated with significant alveolar bone loss in periodontitis mice. Our in vitro study also showed that Porphyromonas gingivalis and high salt stress upregulated the expression of NFAT5 in macrophages, particularly in the nucleus. In addition, NFAT5 interacted with multiple signaling pathways related to cell proliferation, differentiation, and inflammation. Therefore, we hypothesize that NFAT5-regulated macrophage polarization controls alveolar bone loss in periodontitis combined with hypertension. Herein, we will investigate the effect NFAT5-regulated macrophage polarization on alveolar bone loss under high salt stress and inflammatory conditions and explore the mechanism. The results of this study will provide innovative insights into the treatment of patients with periodontitis and hypertension.