染氟成骨细胞中凋亡相关microRNA筛选和鉴定

项目名称： 染氟成骨细胞中凋亡相关microRNA筛选和鉴定

项目编号： No.81460481

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 张亚楼

作者单位： 新疆医科大学

项目金额： 47万元

中文摘要： 饮水型氟中毒由摄入过量氟所致，引起患者关节变形，僵直疼痛，功能障碍，严重危害居民健康，但是致病机制未明。前期研究发现高浓度氟可引起成骨细胞内质网和线粒体肿胀，细胞凋亡，同时发现部分凋亡信号分子表达异常。由于氟能广泛干预成骨细胞内一系列基因表达，而miRNA能调控成骨细胞凋亡，因此提出科学假设：氟对成骨细胞的致凋亡作用，可能与改变miRNA表达有关。本项目分别通过临床病例、氟中毒细胞模型及动物实验，围绕高浓度氟致使成骨细胞凋亡的特点，以凋亡通路为切入点，研究过量氟作用下成骨细胞凋亡过程中表达显著变化的凋亡信号分子和miRNA以二者的相关性，探索miRNA调控凋亡信号分子的机制，明确其在成骨细胞染氟后诱导凋亡的作用。本项目从凋亡受miRNA调控角度来探讨氟中毒致病机制，通过阐明miRNA调控成骨细胞凋亡信号的机理，解释氟骨症中骨细胞凋亡现象，为寻找氟中毒治疗手段提供新的思路和方向。

中文关键词： 地方性氟中毒；成骨细胞；细胞凋亡；微小RNA

英文摘要： Fluorosis （drinking water type） caused by excessive fluoride intake, can cause joint deformation, rigidity pain, dysfunction, which is a serious damage to the residents' health, but even now the pathogenic mechanism is unclear. Previous studies had found that high concentrations of fluoride could cause osteoblast endoplasmic reticulum and mitochondria swelling, and apoptosis. Some abnormal apoptosis signaling molecules expression also were found. Due to fluorine can interfere a series gene expression in the osteoblasts, and the miRNA can regulate osteoblast apoptosis, thus we put forward the scientific hypothesis: fluoride induced apoptosis of osteoblasts, it may be associated with changing the miRNA's expression. through typical clinical cases, animal experiments, and fluorine poisoning cells model in vitro respectively, this project are to study the characteristics of apoptosis in osteoblast caused by high concentration fluoride. Pathway of apoptosis will be as the breakthrough point, we plan to study significant expressions of apoptosis signaling molecules and microRNAs in osteoblast treated with excessive fluoride. correlation between them will also be explored. The mechanism of signaling molecules of apoptosis regulated by microRNAs will be explored to uncover the role of miRNA in apoptosis induced by fluoride. From the angle of apoptosis regulated by the miRNA, this project 's aim is to explore pathogenic mechanism of fluorosis, by illustrating the mechanism of miRNA regulating osteoblast apoptosis signal transduction, and explain how apoptosis appear in the osteoblast in skeletal fluorosis. It also can provide new ideas and directions for new treatment for fluorosis.

英文关键词： endemic fluorosis;osteoblast;apoptosis;microRNA