Single-cell genomic profile of articular chondrocytes from CIA rats

The inflammation of articular cartilage in RA is caused by pro-inflammatory factors secreted by the synovium. However, a recent study has shown that chondrocytes in RA patients can spontaneously secrete pro-inflammatory cytokines and MMPs, which undoubtedly provided new thinking for the treatment of RA diseases. We built a CIA model in rats, took the knee cartilage for single-cell sequencing, and sought to verify whether the contribution of chondrocytes to the inflammatory response in CIA rats was consistent with that of cartilage in RA patients. Our present work is the first to show the genome-wide gene expression of CIA rats cartilage and its assciation with chondrocytes in inflammation response by single-cell RNA sequencing. It was the first time to verify that cartilage destruction in RA disease was involved in the spontaneous inflammation of chondrocytes through CIA model animals. Moreover, the specific pro-inflammatory response cell subtypes have also been identified, which was marked as effector chondrocytes (EC) in the CIA rats cartilage. This not only proved that the cartilage of the CIA rat model can well simulate the inflammatory manifestations of RA patients in vitro, but also provided detailed and complete genomic data for the future study of RA cartilage in vitro.类风湿关节炎（RA，Rheumatoid Arthritis）患者的关节软骨炎症，由滑膜（synovium）分泌的促炎因子所介导。然而近期研究发现，类风湿关节炎患者的软骨细胞（chondrocytes）可自发分泌促炎细胞因子与基质金属蛋白酶（MMPs，Matrix Metalloproteinases），这无疑为类风湿关节炎的疾病治疗提供了全新的研究思路。本研究构建了大鼠胶原诱导性关节炎（CIA，Collagen-Induced Arthritis）模型，提取其膝关节软骨开展单细胞测序（single-cell sequencing），旨在验证软骨细胞在胶原诱导性关节炎大鼠炎症反应中的贡献程度，是否与类风湿关节炎患者软骨的作用一致。本研究首次通过单细胞RNA测序（single-cell RNA sequencing），揭示了胶原诱导性关节炎大鼠软骨的全基因组基因表达谱，及其与软骨细胞炎症反应的关联。本研究首次借助胶原诱导性关节炎动物模型，证实类风湿关节炎的软骨破坏过程与软骨细胞的自发炎症密切相关。此外，本研究还鉴定出一类特异性促炎反应细胞亚型，在胶原诱导性关节炎大鼠软骨中被命名为效应性软骨细胞（EC）。该研究不仅证实大鼠胶原诱导性关节炎模型的软骨可在体外良好模拟类风湿关节炎患者的炎症表现，同时也为未来类风湿关节炎软骨的体外研究提供了详实完整的基因组数据。