脱甲基化酶Jmjd3调节成骨细胞凋亡的作用机制

项目名称： 脱甲基化酶Jmjd3调节成骨细胞凋亡的作用机制

项目编号： No.81500843

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： 杨谛

作者单位： 中国医科大学

项目金额： 18万元

中文摘要： 在慢性根尖周炎的炎症环境下，由于生长因子缺乏引起的成骨细胞的凋亡，是造成根尖周部位病理性骨量减少的原因之一。组蛋白H3第27位赖氨酸残基三甲基化（H3K27me3）调控的表观遗传修饰与基因转录抑制相关。Jmjd3是H3K27me3特定的脱甲基化酶，能够催化H3K27me3转化为H3K27me1，从而使基因转录由抑制状态转变为激活状态。我们首次报道了沉默Jmjd3通过增加转录因子Runx2和Osterix启动子区域H3K27me3的募集水平，从而抑制成骨细胞的分化和骨的形成。Jmjd3是否调控成骨细胞的凋亡过程未见报道。预实验DNA微阵列分析数据表明，沉默Jmjd3降低了抗凋亡蛋白Bcl-2和蛋白激酶D1（PKD1）在成骨细胞中的表达，PKD1通过激活ERK信号通路参与细胞的凋亡过程。本项目将在前期研究结果的基础上，探讨组蛋白脱甲基化酶Jmjd3对成骨细胞凋亡的影响及作用机制。

中文关键词： 慢性根尖周炎；成骨细胞；凋亡；组蛋白脱甲基化酶Jmjd3；表观遗传调控

英文摘要： The apoptosis of osteoblasts resulting from deprivation of cytokines is the main reason for bone loss in the chronic apical periodontitis. Trimethylation of histone H3 lysine 27 (H3K27me3) is an important epigenetic regulation found at the promoters of many genes and is involved in gene silencing. Jumonji domain-containing 3 (Jmjd3), which is a specific histone demethylase for H3K27me3, catalyzes the transition of H3K27me3 to H3K27me1, therefore from a repressive to an active status of gene transcription. Our previous study demonstrated that silencing of Jmjd3 suppressed osteoblast differentiation and bone formation through increasing occupation of H3K27me3 on the promoter regions of transcription factors Runx2 and Osterix. DNA microarray analysis indicated that silencing of Jmjd3 reduced the expressions of Bcl-2 and protein kinase D1(PKD1). The former is an anti-apoptotic protein and the latter is involved in apoptosis through enhancing ERK cell signaling pathway. Based on these data, we try to examine the role of histone demethylase Jmjd3 in osteoblast apoptosis. Understanding the mechanism of epigenetic regulation in osteoblast apoptosis will give us new therapeutic choices for bone loss in chronic apical periodontitis.

英文关键词： chronic apical periodontitis;osteoblast;apoptosis;histone demethylase Jmjd3;epigenetic regulation