Matta Csaba, Takács Roland, Dvir-Ginzberg Mona, Richardson Stephen M, Pelttari Karoliina, Pattappa Girish, Risbud Makarand V, Mobasheri Ali
Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Laboratory of Cartilage Biology, Institute of Bio-Medical and Oral Research, Faculty of Dental Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
Nat Rev Rheumatol. 2025 Jul 10. doi: 10.1038/s41584-025-01275-0.
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.
单细胞多组学技术正在彻底改变软骨细胞生物学，揭示软骨组织内的细胞异质性。尽管过去的研究表明软骨细胞群体中存在细胞异质性，但过去十年单细胞转录组学的进展现在能够对软骨细胞亚型进行更细致、功能注释的分类。这些分析为这些亚型在软骨形成、维持和疾病进展中的作用提供了关键见解。软骨细胞群体与组织稳态、发病机制以及对外部刺激（包括促炎介质和新型治疗药物）的反应有关。这一知识为开发针对骨关节炎和椎间盘疾病等疾病的靶向治疗开辟了途径。对疾病关键软骨细胞群体分子特征的深入了解为生物标志物发现和治疗靶向提供了基础，利用这些发现推进再生疗法也有令人兴奋的机会。细胞标记、行为和代谢活动的时空分析将增强对疾病发病机制和软骨衰老的理解，并有可能实现对骨关节炎的早期干预，从而防止不可逆转的关节损伤。未来的研究必须将先进的单细胞技术与计算模型相结合，以揭示软骨细胞群体的动态相互作用。这些努力可能会改变风湿病学中的精准医学，满足软骨相关疾病中未满足的临床需求。
