11β-HSD1在镉致骨髓间充质干细胞（MSCs）成骨能力异常中的作用研究

项目名称： 11β-HSD1在镉致骨髓间充质干细胞（MSCs）成骨能力异常中的作用研究

项目编号： No.81502842

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 吕颖坚

作者单位： 南方医科大学

项目金额： 18万元

中文摘要： 镉污染引发健康风险备受关注。镉暴露与骨质疏松密切相关，但镉的骨骼毒性机制一直未明确。我们前期研究发现，长期镉暴露的人群尿中活性糖皮质激素皮质酮和四氢可的松含量增高，其代谢关键酶11β-HSD1表达异常可能是重要原因，且11β-HSD1已证实与骨质疏松相关。本研究拟采用体外与体内试验相结合的方法，以成骨细胞的主要来源——骨髓间充质干细胞（MSCs）为研究对象，探讨11β-HSD1在镉致MSCs成骨能力受损中的作用和机制，包括11β-HSD1在MSCs成骨和成脂不同分化阶段的表达；在11β-HSD1沉默和过表达情况下，MSCs成骨和成脂标志基因、成骨过程关键通路分子的激活情况，和活性糖皮质激素及其前体物质的变化水平。本研究结果将为镉的骨骼毒性机制提供新的科学依据。

中文关键词： 11β-羟基类固醇脱氢酶1；镉；骨质疏松；骨髓间充质干细胞

英文摘要： Cadmium (Cd) is an important toxic heavy metal and osteoporosis is associated with Cd pollution. But the mechanism of bone toxicity induced by Cd is not fully elucidated. Our previous study investigated the changes of urine metabolism in a popoulation exposed to environmental Cd pollution, and found that corticosterone and tetrahydrocortisone were upregulated. 11β-HSD1, the key enzyme in glucocorticoid metabolism, might play a critical role. We will study the effect of Cd on mesenchymal stem cells (MSCs), which are the main source of osteoblast. We will analyze protein and gene expression of 11β-HSD1 by Western blot and real-time PCR at different stages along osteogenic and adipogenesis differentiation of MSCs. We will repress or induce 11β-HSD1 expression by specific inhibitor or plasmid transfection, then analyze the marker gene and key molecule expression of osteogenesis pathways, and analyze the hormone and precusor substance levels. We are intend to elucidate the relationship between 11β-HSD1 and osteoporosis induced by Cd, which may finally provide brand new theoretical basis for Cd toxicity.

英文关键词： 11β-HSD1;Cadmium;osteoporosis;mesenchymal stem cells (MSCs)