组蛋白乙酰化/甲基化在口腔疾病中的研究进展  

Research progress on histone acetylation/methylation in oral diseases

作　　者：罗煜川 李飞飞 余钒源 尹贝[1] 叶玲 LUO Yuchuan;LI Feifei;YU Fanyuan;YIN Bei;YE Ling(State Key Laboratory of Oral Diseases&National Center for Stomatology&National Clinical Re-search Center for Oral Diseases&Department of Endodontics,West China Hospital of Stomatology,Sichuan University,Chengdu 610041,China)

机构地区：[1]口腔疾病防治全国重点实验室国家口腔医学中心国家口腔疾病临床医学研究中心四川大学华西口腔医院牙体牙髓科,四川成都610041

出　　处：《口腔疾病防治》2024年第6期463-469,共7页Journal of Prevention and Treatment for Stomatological Diseases

基　　金：国家自然科学基金(81825005,82001019)。

摘　　要：组蛋白乙酰化和甲基化能影响染色质构象,进而调控多种生物学活动。异常的组蛋白乙酰化和甲基化修饰与多种口腔疾病的发生发展有关。在牙的发育过程中,组蛋白乙酰化和甲基化修饰有序地升高或降低,调控牙的发育,氟离子能够破坏组蛋白乙酰化和甲基化修饰的平衡,这可能与氟牙症的发生有关。此外,组蛋白乙酰化和甲基化修饰也参与调控了口腔的炎症性疾病,炎症微环境下,组蛋白乙酰转移酶GCN5表达下降,使Dickkopf 1(DKK1)表达下降,从而激活Wnt/β⁃catenin通路,最终抑制牙周膜干细胞的成骨分化。Zeste增强子同源物2(enhancer of zeste homolog 2,EZH2)与H3K27me3在炎症牙髓组织和牙髓细胞中下降,抑制EZH2可抑制炎症刺激导致的人牙髓细胞中白细胞介素⁃1b、白细胞介素⁃6和白细胞介素⁃8的表达。组蛋白乙酰化/甲基化修饰能够与多条信号通路相互作用,促进口腔肿瘤的发生发展,并与唾液腺肿瘤的高侵袭性有关。靶向组蛋白乙酰化和甲基化相关酶的小分子药物能调控组蛋白甲基化/乙酰化修饰水平,在口腔颌面部疾病治疗中展现出应用潜能,例如组蛋白去乙酰化酶抑制剂——伏立诺他,其既能够抑制炎症的相关细胞因子的分泌,还能促进成牙本质细胞分化并形成牙本质相关基质,展现出了在保髓治疗中的潜力。了解组蛋白乙酰化/甲基化修饰在口腔疾病发生发展中的作用,有助于推进表观遗传修饰在口腔疾病的研究深入,提供新的疾病诊疗视角。Histone acetylation and methylation can affect chromatin conformation and regulate a variety of biological activities.Abnormal histone acetylation and methylation modifications are related to the occurrence and development of a variety of oral diseases.Histone acetylation and methylation increase or decrease in an orderly manner to regulate the development of teeth.Fluoride ions can destroy the balance between histone acetylation and methylation,which may be related to the occurrence of dental fluorosis.In addition,histone acetylation and methylation are involved in the regula⁃tion of oral inflammatory diseases.In the inflammatory microenvironment,the expression of histone acetyltransferase GCN5 decreases,and the expression of Dickkopf 1(DKK1)decreases,activating the Wnt/β⁃catenin pathway and ulti⁃mately inhibiting the osteogenic differentiation of periodontal ligament stem cells.Enhancer of zeste homolog 2(EZH2)and H3K27me3 levels were decreased in inflamed dental pulp tissues and cells.EZH2 inhibition inhibited the expres⁃sion of interleukin(IL)⁃1b,IL⁃6 and IL⁃8 in human dental pulp cells under inflammatory stimulation.Histone acetyla⁃tion/methylation modifications can interact with multiple signaling pathways to promote the occurrence and development of oral tumors and are related to the high invasiveness of salivary gland tumors.Small molecule drugs targeting histone acetylation and methylation⁃related enzymes can regulate the level of histone methylation/acetylation and have shown po⁃tential in the treatment of oral and maxillofacial diseases.For example,the histone deacetylase inhibitor vorinostat can inhibit the secretion of inflammation⁃related cytokines;it also promotes the maturation of odontoblasts and the formation of dentin⁃related matrix,demonstrating its potential in pulp preservation.Understanding the role of histone acetylation/methylation modifications in the occurrence and development of oral diseases will help promote research on epigenetic modifications in oral diseas

关 键 词：组蛋白修饰 组蛋白甲基化 组蛋白去甲基化 组蛋白乙酰化 组蛋白去乙酰化 组蛋白去甲基酶抑制剂 组蛋白去乙酰化酶抑制剂 氟牙症 牙周炎 牙髓炎 

分 类 号：R78[医药卫生—口腔医学]