Single-cell RNA-Seq reveals changes in immune landscape in post-traumatic osteoarthritis. Single-cell RNA-Seq reveals changes in immune landscape in post-traumatic osteoarthritis

Osteoarthritis (OA) is the most common joint disease, affecting over 300 million people world-wide. Accumulating evidence attests to the important roles of immune system in OA pathogenesis. Understanding the role of various immune cells in joint degeneration or joint repair after injury is helpful for improving therapeutic strategies for treating OA. Post-traumatic osteoarthritis (PTOA) develops in ~50% of individuals who have experienced an articular trauma like an anterior cruciate ligament (ACL) rupture. Here, using highly sensitive single-cell RNA sequencing technology, we delineated the temporal dynamics of immune cell accumulation in the mouse knee joint after ACL rupture. Overall design: Right knee joints of 10-week-old C57Bl/6J mice were injured using a tibial compression injury model. Uninjured joints and injured joints from 1-, 3-, 7-, 15- and 30 days post-injury (n=5/group) were collected and immune (Cd45+) cells were analyzed using scRNA-seq. Non-immune (Cd45-) cells from D0 were also profiled using scRNA-seq to determine immune stromal interactions.

骨关节炎 (Osteoarthritis, OA) 是最常见的关节疾病，全球受累人群超3亿。越来越多的研究证据证实，免疫系统在骨关节炎的发病机制中发挥关键作用。阐明各类免疫细胞在关节退变或损伤后关节修复中的功能，有助于优化骨关节炎的治疗方案。创伤后骨关节炎 (Post-traumatic osteoarthritis, PTOA) 在约50%经历过关节创伤（如前交叉韧带 (anterior cruciate ligament, ACL) 撕裂）的个体中发病。本研究采用高灵敏度单细胞RNA测序 (single-cell RNA sequencing) 技术，解析了小鼠膝关节在前交叉韧带撕裂后免疫细胞聚集的时间动态变化。

总体实验设计：本研究通过胫骨压迫损伤模型，对10周龄C57Bl/6J小鼠的右侧膝关节实施造模。分别收集未损伤关节，以及造模后1、3、7、15、30天的损伤关节（每组n=5），借助单细胞RNA测序 (scRNA-seq) 对免疫 (Cd45+) 细胞进行分析。同时对第0天的非免疫 (Cd45-) 细胞开展单细胞RNA测序，以探究免疫细胞与基质细胞的相互作用。