Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen University, 510630 Guangzhou, China; Guangdong Provincial Center for Engineering and Technology Research of Minimally Invasive Spine Surgery, 510630 Guangzhou, China; Guangdong Provincial Center for Quality Control of Minimally Invasive Spine Surgery, 510630 Guangzhou, China.
Department of Rehabilitation Medicine, The Third Affiliated Hospital of Sun Yat-sen University, 510630 Guangzhou, China.
Gene. 2023 Feb 5;852:147063. doi: 10.1016/j.gene.2022.147063. Epub 2022 Nov 22.
Osteoarthritis (OA) is the most common joint disease. Previous studies were focused on general functions of chondrocyte population in OA without elucidating the existence of chondrocyte subpopulations. To investigate the heterogeneity of chondrocyte, here we conducted detailed analysis on the single-cell sequencing data of cartilage cells from OA patients. After quality control, unsupervised K-mean clustering identified seven different subpopulations of chondrocytes in OA. Those subpopulations of chondrocytes were nominated based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis: stress-metabolizing chondrocytes (cluster 1), rhythmic chondrocytes (cluster 2), apoptotic chondrocytes (cluster 3), matrix-synthesis-related chondrocytes (cluster 4), developmental chondrocytes (cluster 5), protein-synthesis-related chondrocytes (cluster 6 and 8), and osteogenesis chondrocytes (cluster 7). We further noticed that the stress-metabolizing chondrocytes (cluster 1) were dominant in early stages of cartilage damage with increased metabolic levels inhibiting cartilage tissue degeneration, while the matrix-synthesis-related chondrocytes (cluster 4) were mainly existed in the late stages of cartilage damage which reorganized collagen fibers with type III collagen disrupting the extracellular matrix and further cartilage damages. Besides, we identified genes NFKBIA and TUBB2B as potential markers for the stress-metabolizing chondrocytes and the matrix synthesis related chondrocytes, respectively. Our study identifies different chondrocyte subpopulations in OA, and highlights the potential different functions of chondrocyte subpopulations in the early versus late stages of cartilage damage.
骨关节炎(OA)是最常见的关节疾病。以前的研究主要集中在软骨细胞群体的一般功能上,而没有阐明软骨细胞亚群的存在。为了研究软骨细胞的异质性,我们对 OA 患者软骨细胞的单细胞测序数据进行了详细分析。在质量控制后,无监督 K-均值聚类在 OA 中鉴定出七种不同的软骨细胞亚群。这些软骨细胞亚群是基于基因本体论和京都基因与基因组百科全书分析命名的:应激代谢性软骨细胞(簇 1)、节律性软骨细胞(簇 2)、凋亡性软骨细胞(簇 3)、基质合成相关软骨细胞(簇 4)、发育性软骨细胞(簇 5)、蛋白质合成相关软骨细胞(簇 6 和 8)和成骨性软骨细胞(簇 7)。我们进一步注意到,应激代谢性软骨细胞(簇 1)在软骨损伤的早期阶段占主导地位,代谢水平升高抑制软骨组织退化,而基质合成相关软骨细胞(簇 4)主要存在于软骨损伤的晚期,重新组织胶原纤维,III 型胶原破坏细胞外基质,进一步损害软骨。此外,我们确定了 NFKBIA 和 TUBB2B 基因作为应激代谢性软骨细胞和基质合成相关软骨细胞的潜在标志物。我们的研究鉴定了 OA 中的不同软骨细胞亚群,并强调了软骨细胞亚群在软骨损伤早期和晚期的潜在不同功能。
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