肌肉骨骼疾病(MSD),包括骨关节炎(OA),骨肉瘤(OS),多发性骨髓瘤(MM),椎间盘退变(IDD),骨质疏松症(OP),和类风湿性关节炎(RA),呈现与疼痛相关的值得注意的障碍,残疾,全球范围内的生活质量受损。近年来,越来越明显的是,N6-甲基腺苷(m6A)是多种生物过程中基因表达的关键调节因子。m6A由0.1-0.4%腺苷酸残基组成,尤其是在翻译终止密码子附近的3'-UTR的开始处。m6A调节器可以分为三种类型,即“作家”,\"reader\",和“橡皮擦”。研究表明,m6A的表观遗传调节影响mRNA加工,核出口,翻译,和拼接。调节细胞死亡(RCD)是细胞在遗传控制下为了维持内环境的稳定而自主有序的死亡。此外,扭曲的RCD被广泛用于影响各种疾病的进程,并受到越来越多的研究者的关注。在过去的几年里,越来越多的证据表明,m6A可以调节基因表达,从而影响不同的RCD过程,在MSD的病因和进化中起着核心作用。目前证实与m6A相关的RCDs是自噬依赖性细胞死亡,凋亡,坏死,焦亡,铁性凋亡,免疫原性细胞死亡,NETotic细胞死亡和凋亡。m6A-RCD轴可以调节软骨细胞的炎症反应和MM细胞对骨重塑的侵袭和迁移能力,从而影响MSD的发展。这篇综述给出了整个肌肉m6A-RCD轴上的调节功能的完整概述,骨头,和软骨。此外,我们还讨论了m6A靶向因子控制RCD的最新进展,并探讨了靶向m6A-RCD的疗法在MSD预防和治疗中的临床应用前景。这些可能为理解MSDs的病理生理机制和临床防治这些疾病提供新的思路和方向。
Musculoskeletal diseases (MSDs), including osteoarthritis (OA), osteosarcoma (OS), multiple myeloma (MM), intervertebral disc degeneration (IDD), osteoporosis (OP), and rheumatoid arthritis (RA), present noteworthy obstacles associated with pain, disability, and impaired quality of life on a global scale. In recent years, it has become increasingly apparent that N6-methyladenosine (m6A) is a key regulator in the expression of genes in a multitude of biological processes. m6A is composed of 0.1-0.4% adenylate residues, especially at the beginning of 3\'-UTR near the translation stop codon. The m6A regulator can be classified into three types, namely the \"writer\", \"reader\", and \"eraser\". Studies have shown that the epigenetic modulation of m6A influences mRNA processing, nuclear export, translation, and splicing. Regulated cell death (RCD) is the autonomous and orderly death of cells under genetic control to maintain the stability of the internal environment. Moreover, distorted RCDs are widely used to influence the course of various diseases and receiving increasing attention from researchers. In the past few years, increasing evidence has indicated that m6A can regulate gene expression and thus influence different RCD processes, which has a central role in the etiology and evolution of MSDs. The RCDs currently confirmed to be associated with m6A are autophagy-dependent cell death, apoptosis, necroptosis, pyroptosis, ferroptosis, immunogenic cell death, NETotic cell death and oxeiptosis. The m6A-RCD axis can regulate the inflammatory response in chondrocytes and the invasive and migratory of MM cells to bone remodeling capacity, thereby influencing the development of MSDs. This review gives a complete overview of the regulatory functions on the m6A-RCD axis across muscle, bone, and cartilage. In addition, we also discuss recent advances in the control of RCD by m6A-targeted factors and explore the clinical application prospects of therapies targeting the m6A-RCD in MSD prevention and treatment. These may provide new ideas and directions for understanding the pathophysiological mechanism of MSDs and the clinical prevention and treatment of these diseases.