Insights into chondrocyte populations in cartilaginous tissues at the single-cell level

Matta, Csaba and Takács, Roland and Dvir-Ginzberg, Mona and Richardson, Stephen M. and Pelttari, Karoliina and Pattappa, Girish and Risbud, Makarand V. and Mobasheri, Ali (2025) Insights into chondrocyte populations in cartilaginous tissues at the single-cell level. NATURE REVIEWS RHEUMATOLOGY, 21 (8). pp. 465-477. ISSN 1759-4790

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Abstract

Chondrocyte biology is being revolutionized by single-cell multi-omics technologies, revealing cellular heterogeneity within cartilaginous tissues. Although past research has implicated cellular heterogeneity in chondrocyte populations, advances over the past decade in single-cell transcriptomics now enable a more granular, functionally annotated classification of chondrocyte subtypes. These analyses provide crucial insights into the role of these subtypes in cartilage formation, maintenance and disease progression. Chondrocyte populations are implicated in tissue homeostasis, pathogenesis and responses to external stimuli, including pro-inflammatory mediators and novel therapeutic agents. This knowledge opens pathways for developing targeted treatments for diseases such as osteoarthritis and intervertebral disc disease. Insights into the molecular signatures of disease-critical chondrocyte populations provide a foundation for biomarker discovery and therapeutic targeting, and there are exciting opportunities for leveraging these findings to progress regenerative therapies. Spatial and temporal profiling of cellular markers, behaviour and metabolic activity will enhance understanding of disease pathogenesis and chondrosenescence and could possibly enable early intervention for osteoarthritis, thereby preventing irreversible joint damage. Future research must integrate advanced single-cell techniques with computational modelling to unravel the dynamic interplay of chondrocyte populations. These efforts could transform precision medicine in rheumatology, addressing the unmet clinical needs in cartilage-related diseases.

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