新型破骨细胞特征性基因的功能鉴定与机制研究

破骨细胞是一类多核的、高度特化的细胞，对骨骼的生长和重建具有重要作用。尽管目前已知多种能够参与调控破骨细胞功能的关键基因，但对破骨细胞功能实现的关键机制依然存在许多未知，且缺乏对不同分化阶段破骨细胞在分子水平上的有效识别。本项目通过建立体外细胞模型结合高通量筛选，发现并初步验证了能够作用破骨细胞功能的新型特征性基因Kbtbd11，拟通过体内外水平鉴定和探索该基因的特征性表达及其分子作用机制，明确其表达的组织特异性和在破骨细胞中功能的独特性；并对其基本功能进行深入挖掘，阐明其作用的分子机制。同时，试图评价该新型破骨细胞功能性基因Kbtbd11是否具备标记基因的特点和应用价值。本项目的完成能为破骨细胞特征性基因增添新认识；为调控破骨细胞的分子机制增添新内容；为破骨细胞谱系的阶段性识别增加新的理论基础；为防治破骨细胞相关的骨代谢疾病增添新的理论靶点。

Osteoclast is a critical cell subset in bone that responsible for skeletal growth and renewal. In current study, many genes have been identified to be involved in regulation of osteoclastic function, but underline mechanisms are not well determined. Besides, there is no better way to identify differentiation stages in osteoclast lineage via molecular markers. Here, we established the cell model of impaired osteoclasts then performed high-throughput screening, we found Kbtbd11 which is a new characteristic gene in high abundance expression in osteoclasts which can regulate osteoclastic function ex vivo and in vivo. We proposed to explore and identify the characteristic expression and significance of this novel gene to clarify the uniqueness and molecular mechanisms of its function in osteoclasts. In addition, we intend to evaluate the characteristics and application of this gene for marking mature osteoclasts. The completion of this project would bring us new understanding to the molecular regulation of osteoclasts, provide theoretical basis for the stage recognition of osteoclast lineage and new potential targets for therapeutic strategies in osteoclast-related diseases.