类端粒沉默干扰体1对骨骼相关疾病的调控作用  

Disrupter of telomeric silencing 1-like in bone-related diseases

作　　者：朱颖 李汉兵[1] 高延盼 Zhu Ying;Li Hanbing;Gao Yanpan(College of Pharmacy,Zhejiang University of Technology,Hangzhou 310014,China;Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province,School of Medicine,Hangzhou City University,Hangzhou 310015,China)

机构地区：[1]浙江工业大学药学院,杭州310014 [2]浙大城市学院医学院,杭州310015

出　　处：《中华老年病研究电子杂志》2024年第4期38-45,共8页Chinese Journal of Geriatrics Research(Electronic Edition)

基　　金：浙江省自然科学基金资助项目(LTGD24H090003);浙江省自然科学基金重点项目(LZ24H310002)

摘　　要：近年来,越来越多的研究表明,表观遗传调控因子在骨骼发育及骨质疏松等骨骼疾病的病理机制中扮演重要作用。其中,组蛋白甲基化水平的调控是热点之一。类端粒沉默干扰体1(DOT1L)是已知催化组蛋白H3K79发生甲基化的唯一酶,其在骨代谢及相关疾病中的作用受到越来越多的关注。DOT1L的表达异常往往引起一系列骨骼系统疾病,例如骨关节炎、骨质疏松症和骨骼发育障碍等,这表明DOT1L在维持骨骼发育及功能稳态方面具有重要作用。此外,也有初步证据表明DOT1L在骨肿瘤发生的潜在作用。从机制上来说,骨关节炎的发病与DOT1L调节的Sirt1/Wnt通路密切相关;骨质疏松的发病与DOT1L对氧化环境调节和对miR-181介导的KAT2B降解调控密不可分。本文综述DOT1L在骨发育进程及骨骼疾病中的作用,以期进一步了解骨骼相关疾病治疗的新靶点和新策略。In recent years,more and more studies have shown that epigenetic regulatory factors play an important role in bone development and bone diseases.Among them,the regulation of histone methylation level is one of the hot topics.Disrupter of telomeric silencing 1-like(DOT1L)is the only enzyme known to catalyze the methylation of histone H3K79.Recently,the role of DOT1L in bone metabolism and related diseases has received much attention.The abnormal expression of DOT1L often causes a series of bone diseases,such as osteoarthritis,osteoporosis and skeletal developmental disorders,which indicates that DOT1L plays an important role in maintaining bone development and functional homeostasis.In addition,there is also preliminary evidence for a potential role of DOT1L in bone tumorigenesis.In terms of mechanism,the pathogenesis of osteoarthritis is closely related to DOT1Lregulated Sirt1/Wnt pathway;the pathogenesis of osteoporosis is closely related to the regulation of oxidative environment and mir181-mediated KAT2B degradation by DOT1L.This article reviews the role of DOT1L in bone development and bone diseases,which provides a new target and treatment strategy for the treatment of bone diseases.

关 键 词：类端粒沉默干扰体1 骨骼发育 骨骼疾病 骨关节炎 骨质疏松 骨肿瘤 

分 类 号：R681[医药卫生—骨科学]