线粒体遗传背景在骨关节炎发生中的作用机制研究

项目名称： 线粒体遗传背景在骨关节炎发生中的作用机制研究

项目编号： No.31501156

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 沈丽君

作者单位： 温州医科大学

项目金额： 20万元

中文摘要： 研究发现线粒体单倍型与包括骨性关节炎（OA）在内的各类退行性疾病的发生有关，但这些研究仅局限在几个特征单倍型的SNP改变来预测疾病的易患性，线粒体特定单倍型在发病过程中的作用机制尚不清楚。我们在前期研究中发现线粒体单倍型G具有增加中国人患膝OA的风险，而单倍型B人群OA风险显著降低。为解释线粒体遗传背景在OA发生发展中的作用，本项目拟通过线粒体敲除及细胞融合技术建立研究模型，对线粒体氧化呼吸活性、拷贝数变化、ROS水平、ATP合成等功能进行检测，首次对基于ATP合成偶联程度和ROS变化的线粒体进化医学假说进行OA相关的功能研究；此外，还将通过表达谱分析来明确线粒体功能存在变化的特定线粒体单倍型是如何通过调动核基因的表达来影响OA的发生；最后，通过OA病人与正常人的软骨细胞进行相关的细胞线粒体功能方面的验证。我们期望通过本研究以明确线粒体单倍型能否作为可靠的生物学标记，以及能否用于临床。

中文关键词： 线粒体单倍型；活性氧（ROS）；呼吸链；骨关节炎；线粒体功能

英文摘要： Mitochondrial haplotypes are associated with degenerative diseases, including osteoarthritis (OA). In order to predict susceptibility of those diseases, the studies carried out before were focused on the SNP(single nucleotide polymorphism) of some specific haplotypes. However, the under lying mechanism of the haplotypes in the development of the diseases remains vague. In the previous research, we found patients carrying haplogroup G had a higher severity progression of knee OA, while people with haplogroup B were less susceptible for OA occurrence. To clarify the mechanism of mitochondrial haplotypes in the development of OA, we are planing to construct fusion cells of different haplogypes, G and B. First, the oxidative respiratory activity of mitochondria, the copy numbers, the reactive oxygen species (ROS) levels, and the ATP synthesis capability are going to be carried out. Then, to clarify the influence of mitochondrial haplotypes in the expression of nuclear genes in the development of OA, we are going to analyse the gene expression profile. At last, to validate, we will detect the mitochondrial function of cells from OA patients compared with cells from normal controls. By doing this research, we hope to make clear that whether the mitochondrial haplotypes can act as reliable biological markers or not , as well as its clinical application.

英文关键词： Mitochondrial haplotype;Reactive oxygen species;Respiratory chain;Osteoarthritis;Mitochondrial function