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.

中文翻译：

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软骨中软骨细胞的单细胞转录组分析与骨关节炎的发病机制

软骨细胞被认为是软骨中唯一的细胞类型。然而，人类关节软骨中软骨细胞的细胞异质性仍不明确，这阻碍了我们对骨关节炎（OA）发病机制的理解。在这里，我们构建了健康软骨中软骨细胞的单细胞转录组图谱，并鉴定了九种软骨细胞亚群，包括稳态软骨细胞、增殖纤维软骨细胞和肥大软骨细胞（HTC）。有趣的是，我们鉴定了两个不同的 HTC 亚群，其中 HTC-1 特异性表达与细胞凋亡和程序性细胞死亡相关的基因。我们确定了软骨细胞的两种主要轨迹，其中一种分化为纤维软骨细胞，而另一种则终止于细胞凋亡。健康软骨和 OA 软骨之间软骨细胞亚群的比较表明，OA 患者中增殖的纤维软骨细胞和 HTC-1 增多，而稳态软骨细胞减少。有趣的是，我们发现了一种 OA 特异性增殖纤维软骨细胞亚群，可能通过炎症促进 OA 的发展。总之，这项研究显着增强了我们对关节软骨中软骨细胞异质性的理解，并为 OA 的发病机制提供了见解。