IL-9调控破骨细胞分化的作用机制及拮抗IL-9促进骨质疏松小鼠钛基内植物骨整合的干预策略

破骨细胞（OC）的数目和功能改变与骨质破坏密切相关，而调控OC功能参与骨溶解的分子机制仍有很多不明了。IL-9是辅助性T细胞分泌因子，文献报道IL-9可保护风湿性关节炎造成的骨质丢失，但是我们却在骨质疏松小鼠血清中检测到IL-9高表达，并且IL-9还可直接促进OC活化。因此，本项目旨在明确IL-9对OC分化的影响及涉及的信号分子，阐明IL-9在不同微环境下调控OC功能参与疾病形成的作用机制，为寻找潜在的疾病干预靶点提供依据。本项目拟利用野生型、IL-9敲基因小鼠及人外周血单个核细胞，从细胞水平探讨IL-9促进OC分化及功能的调控机制；同时建立钛颗粒诱导小鼠颅骨溶解和小鼠卵巢摘除模型，从动物水平探讨IL-9引起不同骨溶解的作用机制；并在此基础上尝试靶向拮抗IL-9促进骨质疏松小鼠钛基内植物骨整合的可能。该项目拓展了IL-9调控OC功能的理论，为骨质破坏相关疾病的诊疗提供了新的思路和策略。

Changes in the number and function of osteoclast（OC）are closely related to bone destruction, while the molecular mechanism regulating the function of OC in osteolysis remains unclear. IL-9 is a secretory factor of T cells, and it has been reported that IL-9 can protect bone loss caused by rheumatoid arthritis. However, in our previous study, high expression of IL-9 was detected in serum of osteoporosis mice, and IL-9 can directly promote OC activation. Therefore, this project aims to clarify the influence of IL-9 on the differentiation of OC, the related signaling molecules, and clarify the mechanism, which IL-9 regulates the function of OC to participate in the formation of disease in different microenvironments, so as to provide a basis for finding potential disease intervention targets. The project intends to use wild-type (WT) mice，IL-9 knockout (IL-9 -/-) littermate mice and human peripheral blood mononuclear cells to explore the regulatory mechanism，whether IL-9 can promote the differentiation and function of OC at the cell level through a variety of biological techniques. At the same time, titanium particle is used to stimulate the mouse skull to induce osteolysis and the mice after OVX (ovariectomized) experiment, to explore the different mechanisms of osteolysis induced by IL-9 at the animal level. On this basis, we try to target the possibility of antagonizing IL-9 and promoting titanium stick bone integration in osteoporotic mice. This project expands the theory that cytokines regulate the function of OC. It provides new ideas and strategies for the diagnosis and treatment of diseases related to bone destruction.