慢性根尖周炎是牙体牙髓病科常见病多发病，其主要的病理特征是破骨细胞介导的炎症性骨吸收，一旦发生不可逆转。申请人前期研究证实，使用单核细胞趋化因子-1（MCP-1）的竞争性抑制剂7ND蛋白可有效干扰体外破骨细胞分化，同时抑制裸鼠体内鳞癌局部骨侵袭进程。这些实验结果为控制炎症性骨吸收提供了新的研究思路。在此工作基础上，本项目拟采用磁珠分选CD14单核细胞建立体外细胞培养模型，检测7ND阻断MCP-1的趋化作用干扰单核细胞的募集迁移，并利用荧光定量PCR、蛋白电泳进一步分析7ND对破骨细胞分化信号通路的影响。同时建立炎症性骨吸收的体内动物模型，结合显微CT扫描、组织学染色及免疫组化验证7ND抑制体内骨吸收的作用。本课题将丰富破骨细胞的研究内容，并期望通过阻断MCP-1的趋化作用控制骨吸收，为探索慢性根尖周炎的早期干预治疗新方法提供理论和实验证据。

Chronic apical periodontities is frequently diagnosed in clinical work of conservative dentistry and endodontics, and its main pathological characteristics are non-stoppable imflammatory bone resorption caused by osteoclasts. Previous studies have shown that a competitive inhibitor of monocyte chemotactic protein-1 (MCP-1), 7 nuclear acid trancted (7ND), could efficiently inhibit the osteoclast differentiation in vitro, and strongly reduced the progression of carcinoma related bone invasion of nude mice. These results supply new directions for researches of controlling inflammatory bone resorption. Based on these work, the current project will establish the cell culture model of osteoclasts by using CD14 magnetic cell separator in vitro, and investigate whether usage of 7ND would block the chemotactic function of MCP-1 and its autocrine mechanisms. The signaling pathways of 7ND inhibiting osteoclast differentiation will also be explored by using real-time PCR and western blotting. Furthermore, an animal model of inflammatory bone resorption will be established by injecting LPS within the calvaria of C57BL/J6 mice, and the local bone resorption will be further tested by utilizing microCT, HE staining and immunohistochemistry. All these information will enrich the research field of osteoclasts, and hope to inhibit osteoclast formation via targeting on MCP-1, which may control inflammatory bone diseases and supply new ways to prevent apical periodontities in future.