Current cutting-edge omics techniques on musculoskeletal tissues and diseases

Abstract

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.

Fig. 1

The timeline of technological developments in exploring musculoskeletal diseases spans multiple biological levels, including transcriptomics, epigenomics, proteomics, and metabolomics

Fig. 2

Application and pipeline of single-cell RNA-seq, single-cell ATAC-seq, and proteomics in OA and RA Cartilage. a Singel-cell RNA-seq. b Single-cell ATAC-seq. c Proteomics

Fig. 3

Application of advanced epigenomics, transcriptomics, proteomics, and metabolomics in cartilage

Fig. 4

Application of advanced epigenomics, transcriptomics, proteomics, and metabolomics in synovium

Fig. 5

Application of advanced transcriptomics and metabolomics in bone cells and bony callus

Fig. 6

Application of advanced transcriptomics, proteomics, and metabolomics in intervertebral disc

Fig. 7

Application of single-cell RNA-seq and spatial transcriptomics in Tendon

Fig. 8

Application of single-cell RNA-seq, single-nucleus RNA-seq, spatial transcriptomics, and metabolomics in muscle