骨质疏松症越发影响老年人的生活质量,课题组前期研究发现肠道激素胰高血糖素样肽-1受体激动剂（GLP-1R）在体内可改善糖尿病及非糖尿病大鼠的骨结构损伤，体外可促进骨髓间充质干细胞及成骨细胞成骨分化，但具体信号通路和作用机制尚未完全阐明。前期结果显示，GLP-1R处理正常人外周血单个核细胞（PBMC）后，CD4+CD25+调节性T细胞（Treg）比例明显升高，而cAMP水平也与CD4+CD25+ Treg细胞的增殖及免疫抑制功能相关，继而推测GLP-1R可能通过cAMP-PKA通路影响体内Treg细胞最终影响骨代谢。本课题拟选用重排活化基因缺失（Rag-1敲除）小鼠作为动物模型，并采用骨质疏松患者PBMC运用细胞培养、分子生物学和细胞移植等技术进一步探讨GLP-1R如何通过cAMP-PKA通路促进Treg细胞增殖分化，并由调节性T细胞改善骨代谢作用机制，为骨质疏松症临床防治提供新的靶点。

With the progress of the aging society, osteoporosis has a serious impact on the quality of life for the elderly. Our preliminary study confirmed that GLP-1R can exert a bone protective effect in both diabetic and non-diabetic osteoporotic rats in vivo, while can facilitate osteoblastogenesis during BMSC and osteoblast lineage differentiation in vitro. However, the exactly signaling pathways involved in the bone effect of GLP-1RA were not fully reported at home and abroad. We found that the population of CD4+CD25+ regular T cells was increased in peripheral blood mononuclear cells after treated with GLP-1R, which were collected from normal humans. While the level of cAMP was closely in relation with the proliferation and immunosuppressive function of regular T cells, we speculated that GLP-1RA may benifit bone metabolism via an effect in the activity of regulatory t cell through the cAMP-PKA pathways. Our research aims to investigate the effects of pathway when GLP-1 receptor agonists on the bone metabolism in vivo and in vitro using the approaches for molecular biology and cell biology. Potentially, our findings may provide a basis for the design of new therapeutic strategy for the intervention of osteoporosis in the clinic.