破骨细胞（OC）功能过度激活是引起骨质疏松症的重要原因，其细胞融合是OC激活、成熟并发挥功能的关键步骤。DC-STAMP是OC融合过程中的核心分子，近期证据提示DC-STAMP启动子去甲基化是促进OC融合的原因，但目前尚无研究阐明该去甲基化过程受何调控。课题组已证实OC融合期去甲基化相关酶TET2蛋白水平显著上调，而靶向其mRNA发挥转录后调控的miR-22呈现下调趋势。预实验提示卵巢切除（OVX）小鼠外周血ciR-015622表达显著上调，结合OC不同分化阶段circRNA表达谱及共表达分析，提示ciR-015622可能与miR-22配对发挥内源性竞争性RNA （ceRNA）作用调控TET2的翻译。本课题拟利用OC体外培养模型证实该ceRNA调控方式，RNA互作证明其靶向关系，采用OVX小鼠模型检测circRNA干预对骨密度的影响，为完善骨质疏松的发病机制和寻找防治新靶点提供理论基础。

Osteoclast (OC) function over-activation is an important cause of osteoporosis. Cell fusion is a key step in OC maturation and function, and increased fusion directly lead to OC function overactivation, DC-STAMP is the most important molecule in OC fusion process. Recent studies suggest that demethylation of DC-STAMP promoter is responsible for promoting OC fusion, but there is no research to explain how the demethylation process is regulated. The level of TET2 protein was significantly up-regulated in OC fusion stage, while miR-22, which regulate TET2 mRNA post-transcriptionally, showed a decreasing expression trend. Microarray expression analysis showed that ciR-015622 may play an endogenous competitive RNA (ceRNA) with miR-22 to regulate the translation of TET2. In addition, the expression of ciR-015622 in peripheral blood of ovariectomized (OVX) mice was significantly up-regulated. This study tend to use in vitro OC model to verify the ceRNA relationship between ciR-015622 and miR-22. OVX osteoporotic mice will be used to test the effects of circRNA on bone density. The aim is to better understand the pathogenesis of osteoporosis and to find a new target for prevention and treatment of osteoporosis.