Li Xiaofei, Fang Liang, Zhou Renpeng, Yao Lutian, Clayton Sade W, Muscat Samantha, Kamm Dakota R, Wang Cuicui, Liu Chuan-Ju, Qin Ling, Tower Robert J, Karner Courtney M, Guilak Farshid, Tang Simon Y, Loiselle Alayna E, Meyer Gretchen A, Shen Jie
Department of Orthopaedic Surgery, Washington University, St. Louis, MO, USA.
Department of Orthopaedics and Rehabilitation, Yale University, New Haven, CT, USA.
Bone Res. 2025 Jun 9;13(1):59. doi: 10.1038/s41413-025-00442-z.
Musculoskeletal disorders, including osteoarthritis, rheumatoid arthritis, osteoporosis, bone fracture, intervertebral disc degeneration, tendinopathy, and myopathy, are prevalent conditions that profoundly impact quality of life and place substantial economic burdens on healthcare systems. Traditional bulk transcriptomics, genomics, proteomics, and metabolomics have played a pivotal role in uncovering disease-associated alterations at the population level. However, these approaches are inherently limited in their ability to resolve cellular heterogeneity or to capture the spatial organization of cells within tissues, thus hindering a comprehensive understanding of the complex cellular and molecular mechanisms underlying these diseases. To address these limitations, advanced single-cell and spatial omics techniques have emerged in recent years, offering unparalleled resolution for investigating cellular diversity, tissue microenvironments, and biomolecular interactions within musculoskeletal tissues. These cutting-edge techniques enable the detailed mapping of the molecular landscapes in diseased tissues, providing transformative insights into pathophysiological processes at both the single-cell and spatial levels. This review presents a comprehensive overview of the latest omics technologies as applied to musculoskeletal research, with a particular focus on their potential to revolutionize our understanding of disease mechanisms. Additionally, we explore the power of multi-omics integration in identifying novel therapeutic targets and highlight key challenges that must be overcome to successfully translate these advancements into clinical applications.
肌肉骨骼疾病，包括骨关节炎、类风湿性关节炎、骨质疏松症、骨折、椎间盘退变、肌腱病和肌病，是普遍存在的疾病，对生活质量有深远影响，并给医疗系统带来巨大经济负担。传统的整体转录组学、基因组学、蛋白质组学和代谢组学在揭示人群水平上与疾病相关的改变方面发挥了关键作用。然而，这些方法在解析细胞异质性或捕捉组织内细胞的空间组织方面存在固有限制，从而阻碍了对这些疾病潜在的复杂细胞和分子机制的全面理解。为了解决这些限制，近年来出现了先进的单细胞和空间组学技术，为研究肌肉骨骼组织内的细胞多样性、组织微环境和生物分子相互作用提供了无与伦比的分辨率。这些前沿技术能够详细绘制患病组织中的分子图谱，在单细胞和空间水平上为病理生理过程提供变革性的见解。本综述全面概述了应用于肌肉骨骼研究的最新组学技术，特别关注它们在彻底改变我们对疾病机制理解方面的潜力。此外，我们探讨了多组学整合在识别新型治疗靶点方面的作用，并强调了将这些进展成功转化为临床应用必须克服的关键挑战。
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