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N6-甲基腺苷在骨关节炎发病机制及临床治疗中调节作用的新见解:研究现状与展望

Novel Insights into the Regulatory Role of N6-Methyladenosine in the Pathogenesis and Clinical Treatment of Osteoarthritis: Research Status and Prospect.

作者信息

He Mingyu, Liu Jian, Sun Yanqiu, Fang Yanyan, Wang Fanfan

机构信息

Department of Rheumatology, the First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui Province, People's Republic of China.

出版信息

J Inflamm Res. 2025 May 27;18:6749-6766. doi: 10.2147/JIR.S508973. eCollection 2025.

Abstract

Osteoarthritis (OA) is caused by characteristic joint tissue lesions characterized by chronic joint pain, stiffness, and limited mobility. OA is one of the most common causes of chronic disability in adults, seriously affecting the quality of life of patients and causing huge medical and socio-economic burdens. N6-methyladenosine (m6A) is a methylation that occurs at the N6 position of adenosine and is the most common chemical modification on eukaryotic RNA. m6A modification is a dynamic regulation process involving "writers" (methyltransferases), "erasers" (demethylases), and "readers" (reading proteins). Disruption or interference of this dynamic modification may lead to dysregulation of cellular regulatory mechanisms, resulting in various diseases. This article summarized the regulatory mechanism of m6A modification in OA pathogenesis, including regulation of inflammatory response and immune infiltration, extracellular matrix (ECM) degradation, programmed cell death, bone homeostasis, and osteogenic differentiation. Finally, the application and future development prospects of m6A modification in the clinical treatment of OA were further discussed.

摘要

骨关节炎(OA)是由以慢性关节疼痛、僵硬和活动受限为特征的关节组织病变引起的。OA是成人慢性残疾最常见的原因之一,严重影响患者的生活质量,并造成巨大的医疗和社会经济负担。N6-甲基腺苷(m6A)是一种发生在腺苷N6位置的甲基化,是真核RNA上最常见的化学修饰。m6A修饰是一个动态调控过程,涉及“书写器”(甲基转移酶)、“擦除器”(去甲基化酶)和“阅读器”(阅读蛋白)。这种动态修饰的破坏或干扰可能导致细胞调节机制失调,从而引发各种疾病。本文综述了m6A修饰在OA发病机制中的调控机制,包括对炎症反应和免疫浸润、细胞外基质(ECM)降解、程序性细胞死亡、骨稳态和成骨分化的调控。最后,进一步讨论了m6A修饰在OA临床治疗中的应用及未来发展前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6515/12126110/1aaff4c499a4/JIR-18-6749-g0001.jpg

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