干扰素调节因子5调控巨噬细胞焦亡与根尖周骨破坏

巨噬细胞焦亡(Pyroptosis)是一种特殊的促炎型程序性细胞死亡方式，在介导炎症和免疫反应中扮演重要角色，但其对骨代谢的作用效应和机理尚不明确。近来有研究指出糖酵解对巨噬细胞焦亡发生起着重要的“门控效应”。在前期研究基础上，课题组发现根尖周病损区存在巨噬细胞焦亡显著活化，可能与IRF5及糖酵解信号上调密切相关。因此提出“IRF5通过干预糖酵解信号调控巨噬细胞焦亡进而影响根尖周骨破坏”的科学假说。通过人根尖周病变组织、动物模型及条件性基因敲除小鼠等，探讨IRF5、糖酵解信号及巨噬细胞焦亡与根尖周病中的关系；利用糖酵解阻断剂2-DG明确巨噬细胞焦亡抑制对小鼠根尖周炎的治疗效应；将IRF5及糖酵解信号干预下的焦亡巨噬细胞分别与破骨细胞、成骨细胞共培养，以探讨其参与根尖周骨代谢的作用机理。研究结果将为揭示巨噬细胞参与根尖周病骨破坏的机制提供新的理论依据，并为炎性溶骨性疾病的治疗提供新的思路。

Macrophage pyroptosis is a distinct inflammatory programmed cell death, and plays essential roles in autoimmune and inflammatory diseases. However, the effect and related mechanisms of macrophage pyroptosis on bone metabolism remains unclear. Latest studies point out that glycolysis is closely related with macrophage pyroptosis. Our preliminary data also indicated that macrophage pyroptosis was activated in periapical lesions, which was involved in IRF5 and glycolysis signaling. Thus, we formulate a hypothesis that IRF5 regulates macrophage pyroptosis via glycolysis and affects the progression of periapical bone resorption. Therefore,the present project is designed to investigate:(1) IRF5 expression, glycolysis and macrophage pyroptosis in clinical periapical tissues and in conditional knockout mice.(2) the effect of 2-DG inhibiting glycolysis on macrophage pyroptosis during periapical lesions progression. (3) the biological characteristics assessment of osteoclasts and osteoblasts, which are respectively co-cultured with the macrophage showing pyroptosis. Achievements of this project will contribute to a deeper molecular understanding of macrophage-mediated periapical lesions, and provide new insight into potential strategies for the relevant treatment of osteolytic diseases.