Wnt7b调控破骨细胞分化及骨吸收功能的机制研究

根尖周病变导致的骨丢失是牙髓根尖周病的常见预后，根尖周局部牙槽骨的破骨增强和成骨抑制是主要机制，其愈合依赖于感染的清除和新骨的形成。难治性根尖周炎常表现为根尖周骨质的进行性破坏吸收，破骨功能的亢进是其可能的原因且机制尚未完全清楚。课题组前期研究发现Wnt7b在促进骨修复的同时可以抑制骨吸收和破骨细胞分化，但后者的具体作用机制尚不可知。因此本题目拟结合转基因小鼠技术、Cas9体外基因干预技术、高通量测序及分子生物学手段探究Wnt7b调控破骨细胞分化的分子机制；同时拟局部采用富Wnt7b材料，研究其用于治疗根尖周骨修复的有效性和安全性，进一步验证Wnt7b应用于根尖周病治疗的可行性。本课题有望能阐明Wnt7b调控破骨细胞分化及骨吸收功能的作用机制，并为其应用于根尖周骨修复治疗提供实验基础，也为治疗根尖周病提供新的思路。

Periapical bone loss is the common result of endodontic diseases, which is mainly caused by local inhibited bone formation and increased bone resorption. The healing of periapical bone loss can result from the infection control and formation of new bone. refractory apical periodontitis are demonstrated as aggressive bone resorption, which might be explained by the enhanced osteoclastogenesis, while the underlying mechanism remains largely unknown. Our previous work has shown that Wnt7b could promote the bone formation as well as inhibit bone resorption, with the molecular mechanism of the latter needs to be elucidated. In this project, we aim to study the biological function of Wnt7b on osteoclast differentiation and its function, by using transgenic mice, CRISPR/Cas9 technique, high input sequencing and Chip-seq, etc. We also plan to explore the possibility of using Wnt7b locally to promote the healing of periapical bone loss. Our research might shed new light on the molecular regulation of osteoclastogenesis and provide treatment target for future endodontic treatment.