ClC-3氯通道介导甲状旁腺激素对成骨细胞的作用及机制研究

项目名称： ClC-3氯通道介导甲状旁腺激素对成骨细胞的作用及机制研究

项目编号： No.81200648

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 王欢

作者单位： 中国人民解放军第四军医大学

项目金额： 23万元

中文摘要： 骨质疏松是老龄化社会面临的重要健康问题。甲状旁腺激素（PTH）作为体内调节骨代谢的重要激素，因作用机制复杂且尚不明确，严重影响其在骨质疏松及其它骨病中的临床应用。ClC-3为电压门控型氯通道之一，近年研究表明其作用不仅局限于细胞容积调控和酸化调节，还与细胞增殖、凋亡、破骨细胞的功能相关。有研究发现，Clcn3基因敲除小鼠表现出骨代谢异常，我们前期研究也发现ClC-3在多种成骨谱系细胞中均有表达并能促进成骨细胞的分化，进一步发现PTH刺激下ClC-3发生显著变化，是否ClC-3介导了PTH在成骨细胞中的作用还不清楚。因此，本项目在前期工作基础上，拟通过基因转染、siRNA、免疫荧光、Micro CT等技术体外及体内探讨ClC-3在成骨细胞中介导PTH刺激及下游信号的作用机制，为PTH在骨代谢中的作用机制研究开辟新的思路，同时为使用离子通道药物设计骨代谢疾病新的治疗靶点提供理论依据。

中文关键词： 氯通道；甲状旁腺激素；成骨细胞；转化生长因子；

英文摘要： Osteoporosis is one of the most important health problems in the aging society. Parathyroid hormone(PTH) is one of the important hormones which regulates calcium homeostasis．PTH has dual effects on bone metabolism.Intermittent administration of PTH induces bone formation，but the mechanism is unclear．Because of the complicated and unclear mechanism of PTH in bone metabolism, the application of PTH in osteoporosis and other related diseases is limited. ClC-3 chloride channel has been speculated to contribute to the acidification of synaptic vesicles and endosomes. Clcn3-/- mice are smaller than their littermates soon after birth, and exhibited skeletal abnormality, such as kyphoscoliosis, developmental retardation, abnormal metabolism of calcium and phosphorus and higher mortality.In previous study, we first analyzed ClC-3 expression in MC3T3-E1 cells and primary mouse osteoblasts and demonstrated the function of ClC-3 in osteodifferentiation. We also found that PTH promoted the expression of ClC-3 in osteoblasts.Therefore,we hypothesize that PTH promote osteogenic differentiation through ClC-3. In the study, we will focalize on ClC-3 to research the mechanism of promotion of PTH in osteogenesis using gene transfection, RNA iterference, real-time PCR, western blot and immumofluorescence method. Animal experiments

英文关键词： ClC-3 chloride channel；parathyroid hormone；osteoblast；TGF-β1 signal pathway；