mettl3介导的m6A RNA甲基化在协调肌肉骨骼发育中的关键作用：潜在机制和治疗观点

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell Pub Date : 2025-08-22 DOI:10.1016/j.tice.2025.103098

Yuanzhong Liang, Yang Fan, Chang Liu

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引用次数: 0

摘要

肌肉骨骼系统提供结构支持并使运动，依赖于复杂的发育过程，由转录和转录后机制协调。其中，n6 -甲基腺苷（m6A） RNA甲基化主要由甲基转移酶样3 （METTL3）催化，已成为影响细胞分化和功能的基因表达的关键调节因子。本文综述了目前阐明mettl3介导的m6A修饰在肌肉骨骼发育中不可或缺的作用的证据。我们详细介绍了METTL3如何通过mrna（如MEF2C、MyoD、MNK2、ACVR2A）和非编码rna（如miRNAs、lncRNAs、circRNAs）的靶向甲基化来控制骨骼肌细胞中的关键事件，包括卫星细胞激活、成肌细胞增殖和分化、肌管形成和再生。同样，METTL3通过指导骨髓基质细胞的成骨分化、成骨细胞的功能、破骨细胞的分化和活性以及软骨细胞的稳态，对骨细胞动力学进行关键调控。METTL3表达或功能的破坏会损害肌肉和骨骼的发育和修复。这一综合分析强调了METTL3作为协调肌肉骨骼形成和维持的中心表观遗传调控因子。此外，我们讨论了靶向METTL3及其相关途径在治疗肌肉骨骼损伤和疾病的再生医学策略中的重要转化潜力。

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The critical role of METTL3-mediated m6A RNA methylation in orchestrating musculoskeletal development: Underlying mechanisms and therapeutic perspectives

The musculoskeletal system provides structural support and enables movement, relying on intricate developmental processes coordinated by transcriptional and post-transcriptional mechanisms. Among these, N⁶-methyladenosine (m⁶A) RNA methylation, catalyzed primarily by methyltransferase-like 3 (METTL3), has emerged as a crucial regulator of gene expression impacting cellular differentiation and function. This review synthesizes current evidence elucidating the indispensable role of METTL3-mediated m⁶A modification in musculoskeletal development. We detail how METTL3 governs key events in skeletal muscle cells, including satellite cell activation, myoblast proliferation and differentiation, myotube formation, and regeneration, through targeted methylation of mRNAs (e.g., MEF2C, MyoD, MNK2, ACVR2A) and non-coding RNAs (e.g., miRNAs, lncRNAs, circRNAs). Similarly, METTL3 critically regulates bone cell dynamics by directing the osteogenic differentiation of bone marrow stromal cells, osteoblast function, osteoclast differentiation and activity, and chondrocyte homeostasis. Disruption of METTL3 expression or function impairs both muscle and bone development and repair. This comprehensive analysis underscores METTL3 as a central epigenetic regulator coordinating musculoskeletal formation and maintenance. Furthermore, we discuss the significant translational potential of targeting METTL3 and its associated pathways for regenerative medicine strategies aimed at treating musculoskeletal injuries and disorders.

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来源期刊

Tissue & cell 医学-解剖学与形态学

CiteScore

3.90

自引率

0.00%

发文量

234

期刊介绍： Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.