RNA m^(6)A甲基化修饰参与及调控骨科相关疾病  

N6-methyladenosine RNA methylation is involved in orthopedic related diseases

作　　者：陈伟坚 张罡瑜 林天烨 梁笃[1] 王海彬[3] Chen Weijian;Zhang Gangyu;Lin Tianye;Liang Du;Wang Haibin(Guangzhou Bone Setting Hospital affiliated to Guangzhou University of Chinese Medicine,Guangzhou 510405,Guangdong Province,China;The First Clinical Medical College of Guangzhou University of Chinese Medicine,Guangzhou 510405,Guangdong Province,China;Department of Orthopedics,The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405,Guangdong Province,China)

机构地区：[1]广州中医药大学附属广州市正骨医院,广东省广州市510405 [2]广州中医药大学第一临床医学院,广东省广州市510405 [3]广州中医药大学第一附属医院骨科,广东省广州市510405

出　　处：《中国组织工程研究》2021年第26期4236-4242,共7页Chinese Journal of Tissue Engineering Research

基　　金：2017年国家自然科学基金面上项目(81774339),项目负责人:王海彬;2020年国家自然科学基金面上项目(82074462),项目负责人:王海彬。

摘　　要：背景:随着高通量测序技术的发展,研究发现骨髓间充质干细胞、成骨细胞、脂肪细胞、破骨细胞、软骨细胞和骨肉瘤细胞等均可检测到m^(6)A修饰的存在,m^(6)A修饰可通过调控细胞RNA水平的甲基化,影响相关基因的mRNA和(或)非编码RNA的翻译等过程,从而激活细胞信号转导通路,影响细胞的增殖、分化、迁移、侵袭、凋亡及DNA损伤修复等,进而调控骨骼发育、关节退变、骨折愈合及骨肿瘤的发生、发展等生理病理过程。目的:总结近年来m^(6)A修饰在骨质疏松症、骨关节炎等骨科疾病中的最新研究成果和作用机制,为开发骨科相关疾病的新型治疗策略提供启发。方法:以中文关键词“N6-甲基腺嘌呤,骨质疏松症,骨关节炎,骨科疾病”检索CNKI数据库,以英文关键词“m^(6)A,osteoporosis,osteoarthritis,orthopedic disease”检索PubMed数据库,全网检索自建库至2020年6月有关m^(6)A修饰在骨科疾病中研究成果的文献,严格按照纳入和排除标准筛选,最后选定61篇文献进行综述。结果与结论:①在骨质疏松症进展过程中,METTL3/m^(6)A介导的RNA甲基化以及FTO/m^(6)A介导的RNA去甲基化动态调控相关基因的表达,进一步影响相关信号通路的激活,影响骨髓间充质干细胞的成骨及成脂分化;②METTL3/m^(6)A通过调节软骨细胞中的核因子κB信号传导和细胞外基质合成,在骨关节炎进展中“扮演”了重要的角色;③METTL3/m^(6)A通过靶向调控成骨细胞相关的miR-7212-5p来抑制骨折愈合过程中的成骨机制;④METTL3通过调节淋巴增强因子1的m^(6)A水平从而激活Wnt/β-catenin信号以及通过调节ATAD2基因的m^(6)A甲基化来加速骨肉瘤的恶化;⑤在骨质疏松症、骨关节炎等骨科疾病中,m^(6)A修饰均参与了多系统疾病的进程,m^(6)A修饰的深入研究为进一步了解骨科相关疾病的发病机制提供了理论依据,并提供了基于表观遗传学基础的骨科疾病BACKGROUND:With the development of high-throughput sequencing technology,recent studies have found that the presence of N6-methyladenosine(m^(6)A)modification can be detected in bone marrow mesenchymal stem cells,osteoblasts,adipocytes,osteoclasts,chondrocytes,and osteosarcoma cells.It can affect the translation of mRNA and/or non-coding RNA of related genes by regulating the methylation of RNA in cells,which can activate cell signal transduction pathways,regulating cell proliferation,differentiation,migration,invasion,apoptosis and DNA damage repair.In turn,it can regulate the physiological and pathological processes such as bone development,joint degeneration,fracture healing,and the occurrence and development of bone tumors.OBJECTIVE:To summarize the latest research results and specific mechanisms of m^(6)A modification in osteoporosis,osteoarthritis and other orthopedic diseases in recent years,and to offer inspiration for the development of new treatment strategies for orthopedic diseases.METHODS:CNKI and PubMed were searched with the keywords of“N-6 methyladenine,osteoporosis,osteoarthritis,orthopedic diseases”for literatures regarding m^(6)A methylation modification in orthopedic diseases from their inception date to June 2020.According to the established inclusion and exclusion criteria,61 articles were finally included for review.RESULTS AND CONCLUSION:During the accelerated development of osteoporosis,METTL3-mediated m^(6)A methylation and FTO-mediated m^(6)A demethylation affect the expression of related genes and further regulate the bone formation and adipogenic differentiation of bone marrow mesenchymal stem cells.METTL3-mediated m^(6)A methylation plays an important role in the development of osteoarthritis by regulating nuclear-κB signaling in chondrocytes and extracellular matrix synthesis.METTL3/m^(6)A inhibits the osteogenic mechanism in the fracture healing process by targeting the regulation of osteoblast-related miR-7212-5p.METTL3 activates Wnt/β-catenin signals by regulating the m^(6)

关 键 词：RNA m^(6)A修饰 m^(6)A修饰酶系统 骨骼发育 成骨 脂肪 软骨 骨质疏松症 骨关节炎 骨肉瘤 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学]