DNA甲基化在颞下颌关节骨关节炎发病机制中作用的研究

项目名称： DNA甲基化在颞下颌关节骨关节炎发病机制中作用的研究

项目编号： No.31271548

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 孟娟红

作者单位： 北京大学

项目金额： 80万元

中文摘要： 颞下颌关节骨关节炎 (temporomandibular joint osteoarthritis, TMJ-OA)是临床常见病，其发病机制尚不完全明确，治疗效果亦不理想。本课题组以往研究表明TMJ-OA是一有多基因参与的复杂性疾病。随着表观遗传学在人类疾病发病机制和治疗方面研究越来越引起重视，表观遗传调节与OA关系的研究成为近几年OA发病机制研究中的一个新视点。DNA甲基化是最重要的表观调节机制之一。本研究拟通过已构建的TMJ-OA动物模型，比较OA与正常髁突软骨全基因组水平DNA甲基化修饰模式的差异；选择与OA发病相关、甲基化变异明显的基因，观察其基因的表达变化，分析DNA甲基化与基因表达变化之间的关系；采用原代髁突软骨细胞和软骨细胞系进一步对特定基因的甲基化位点进行初步的调控研究。通过以上研究评价DNA甲基化在TMJ-OA发病机制中的作用，以期为该病治疗提出新的治疗策略和实验依据。

中文关键词： 颞下颌关节；骨关节炎；DNA 甲基化；表观遗传；软骨细胞

英文摘要： Temporomandibular joint osteoarthritis (TMJ-OA) is a common clinical disease in the oral and maxillofacial area. Since its pathogenesis is unclear, the treatment effect is not ideal. Our previous studies showed that TMJ-OA is a complex disease which multiple genes could be involved in. With its study in the pathogenesis and treatment of some human diseases, epigenetics has drawn more and more attention in recent years. DNA methylation is one of the most important epigenetic modifications. Aberrant methylation patterns are involved in important pathologies such as tumorigenesis and some complex diseases. The relationship between epigenetic regulation and OA is a new sight in OA pathogenesis research. In the present study, a genome-wide DNA methylation modification pattern between OA and normal cartilages will be detected by methylated DNA immunoprecipitation sequencing based on our previous TMJ-OA animal models, and the data will be further analyzed; combined with our previous Genechip results about differential gene expression pattern, the significant DNA methylation sites will be selected for further observing the change of its gene expression and analyzing of the relationship between DNA methylation and gene expression; primary condylar chondrocyte and chondrocyte cell line are further studied about the methyl

英文关键词： Temporomandibular joint；Osteoarthritis；DNA methylation；Epigenetic；Chondrocytes