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个体运动功能的分子基础：对肌肉骨骼系统发育和稳态中基因表达调控的综合理解。

Molecular basis of individual locomotor function: Integrated understanding of gene expression regulation in the development and homeostasis of the musculoskeletal system.

作者信息

Asahara Hiroshi

机构信息

Department of Systems BioMedicine, Graduate School of Medical and Dental Sciences.

Department of Molecular and Cellular Biology, The Scripps Research Institute.

出版信息

Proc Jpn Acad Ser B Phys Biol Sci. 2025;101(7):373-393. doi: 10.2183/pjab.101.027.

DOI:10.2183/pjab.101.027
PMID:40721379
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12463553/
Abstract

This review examines the molecular mechanisms controlling the development and homeostasis of the musculoskeletal system through gene expression regulation. It introduces key discoveries from basic transcriptional control to advanced mechanotransduction pathways, focusing on our contributions including the EMBRYS database for transcription factor expression analysis and the identification of RP58 in muscle development and Mohawk (Mkx) in tendon formation. We also elucidated the role of miR-140 as a critical regulator in cartilage development and homeostasis. This microRNA is specifically expressed in cartilage, promotes chondrogenesis, and is involved in protective mechanisms against cartilage degenerative diseases such as osteoarthritis. Our discovery of the PIEZO1-Mkx pathway provides a molecular mechanism linking mechanical stimuli to gene expression in tendons, explaining tissue adaptation and differences in motor abilities. Understanding these pathways offers new therapeutic strategies for tendon and ligament injuries, age-related decline, and cartilage diseases. Currently, we are proposing the concept of "tenopenia" to complement sarcopenia, addressing the mechanisms of age-related tendon deterioration. This integrated approach to the musculoskeletal system as an environment-responsive entity advances both fundamental science and clinical applications aimed at maintaining mobility throughout life.

摘要

本综述通过基因表达调控研究了控制肌肉骨骼系统发育和稳态的分子机制。它介绍了从基本转录控制到先进机械转导途径的关键发现，重点阐述了我们的贡献，包括用于转录因子表达分析的EMBRYS数据库，以及在肌肉发育中鉴定出的RP58和在肌腱形成中鉴定出的莫霍克（Mkx）。我们还阐明了miR-140作为软骨发育和稳态关键调节因子的作用。这种微小RNA在软骨中特异性表达，促进软骨形成，并参与针对骨关节炎等软骨退行性疾病的保护机制。我们发现的PIEZO1-Mkx途径提供了一种将机械刺激与肌腱中基因表达联系起来的分子机制，解释了组织适应性和运动能力差异。了解这些途径为肌腱和韧带损伤、与年龄相关的衰退以及软骨疾病提供了新的治疗策略。目前，我们提出了“肌腱减少症”的概念以补充肌肉减少症，探讨与年龄相关的肌腱退化机制。这种将肌肉骨骼系统视为对环境有反应的实体的综合方法推动了旨在维持终身活动能力的基础科学和临床应用的发展。

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