国际口腔医学杂志 ›› 2019, Vol. 46 ›› Issue (5): 593-603.doi: 10.7518/gjkq.2019056

• 综述 • 上一篇    下一篇

甲基化对牙周炎发生与发展的影响及临床应用

姜亦洋,刘怡()   

  1. 首都医科大学附属北京口腔医院牙周科,全牙再生与口腔组织功能重建北京市重点实验室,组织再生免疫学实验室 北京 100050
  • 收稿日期:2018-09-20 修回日期:2019-04-05 出版日期:2019-09-01 发布日期:2019-09-10
  • 通讯作者: 刘怡
  • 作者简介:姜亦洋,硕士,Email: 15901135199@163.com
  • 基金资助:
    首都卫生发展科研专项项目(2016-2-2141)

Effects of methylation on the occurrence and development of periodontitis and its clinical application

Jiang Yiyang,Liu Yi()   

  1. Laboratory of Tissue Regeneration and Immunology and Dept. of Periodontics, Beijing Key Laboratory for Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing 100050, China
  • Received:2018-09-20 Revised:2019-04-05 Online:2019-09-01 Published:2019-09-10
  • Contact: Yi Liu
  • Supported by:
    This study was supported by Capital Medical Development Research Fund Project(2016-2-2141)

摘要:

牙周炎主要是由局部因素引起的牙周支持组织的慢性炎症,细菌感染与宿主免疫反应之间的抗衡影响着疾病的发生、发展。甲基化作为表观遗传修饰的一种,在这其中起到了举足轻重的作用,也成为近年来的热点,它可通过改变染色质的结构选择性地激活或抑制某些基因,影响炎症过程中炎性因子、信号分子、细胞外基质分子的表达,进而调控宿主的免疫水平。对甲基化模式的研究不仅可以增加人们对牙周炎的认识,也对临床有着深远的意义,有助于人们探索治疗牙周炎的新途径,改善牙周炎的预后和转归,是未来重要的研究内容。本文从甲基化修饰的角度对牙周炎相关的研究进展作一综述。

关键词: 甲基化, 牙周炎, 细胞因子

Abstract:

Periodontitis is a chronic inflammation of the supporting periodontal tissues caused by local factors. The counterbalance between bacterial infection and host immune response influences the occurrence and development of this disease. As a kind of epigenetic modification, methylation plays a critical role in this process and has become a research hotspot in recent years. Methylation can activate or inhibit certain genes by altering the structure of chromatin, thereby affecting the expression of inflammatory factors, signaling molecules, and extracellular matrix molecules during inflammation. Thus, methylation can regulate host immunity. Studying methylation patterns can contribute to the public understanding of periodontitis and have profound clinical significance. New ways to treat periodontitis and improve its prognosis need to be explored. This article reviews the research progress of periodontitis from the perspective of methylation modification.

Key words: methylation, periodontitis, cytokine

中图分类号: 

  • R781.4

图 1

DNA甲基化机制 DNA甲基化普遍发生在DNA链中的CpG二核苷酸上,这些CpG岛主要位于基因的启动子区域。当调控区发生甲基化时,由甲基转移酶介导,CpG位点上发生特定序列的甲基化,导致DNA结构浓缩,从而干扰转录因子进入启动子区域,使基因沉默、抑制转录。而当调控区未发生甲基化时,启动子区域的DNA能暴露出与转录因子相结合的位点,使转录正常进行、基因表达正常。"

图 2

DNA甲基化影响TLR介导的细胞内信号通路 牙周炎病原微生物表面存在大量的LPS,当细菌入侵机体时,LPS被巨噬细胞、树突状细胞、牙龈上皮细胞表面的TLR-2和TLR-4识别,激活宿主免疫应答。其中在TLR受体激活的信号通路中,DNA甲基化起了关键调控作用。在牙周炎患者中,TLR基因中的CpG位点存在不同的DNA甲基化,这些位点位于启动子区域NF-κB结合位点的周围,DNA甲基化的改变可以影响NF-κB与启动子的结合,从而影响TLR的表达,并会进一步影响宿主产生促炎性细胞因子,如IL-1、IL-6、IL-8和TNF-α,调节和改变宿主免疫,从而影响牙周炎的进展。"

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