Single-cell transcriptomic analysis of chondrocytes in cartilage and pathogenesis of osteoarthritis

Chondrocyte is considered the only cell type in cartilage. However, the cell heterogeneity of chondrocytes in human articular cartilage is still not well defined, which hinders our understanding of the pathogenesis of osteoarthritis (OA). Here, we constructed a single-cell transcriptomic atlas of chondrocytes in healthy cartilage and identified nine chondrocyte subsets including homeostatic chondrocytes, proliferate fibrochondrocytes, and hypertrophic chondrocytes (HTC). Interestingly, we identified two distinct HTC subpopulations, among which HTC-1 specifically expressed genes associated with apoptosis and programmed cell death. We identified two main trajectories of chondrocytes, one of which differentiates into fibrochondrocytes, while the other terminates in apoptosis. Comparison of chondrocyte subsets between healthy and OA cartilage showed that proliferate fibrochondrocytes and HTC-1 expanded in OA patients, whereas homeostatic chondrocytes decreased. Interestingly, we discovered an OA-specific proliferate fibrochondrocyte subset that may contribute to the development of OA via inflammation. In summary, this study significantly enhanced our understanding of cell heterogeneity of chondrocytes in articular cartilage and provides insight into the pathogenesis of OA.