Department of Orthopedics, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
Institute of Sports Medicine and Health, Qingdao University, Qingdao, Shandong, China.
Front Immunol. 2023 Aug 16;14:1247355. doi: 10.3389/fimmu.2023.1247355. eCollection 2023.
Rheumatoid arthritis (RA) is a common autoimmune joint disease, the pathogenesis of which is still unclear. Cartilage damage is one of the main manifestations of the disease. Chondrocytes are the main functional component of articular cartilage, which is relevant to disease progression. Mechanical loading affects the structure and function of articular cartilage and chondrocytes, but the effect of weight bearing on chondrocytes in rheumatoid arthritis is still unclear.
In this paper, single-cell RNA sequencing (scRNA-seq) was performed on collected cartilage from the weight-bearing region (Fb group) and non-weight-bearing region (Fnb group) of the femur, and the differences between the Fb and Fnb groups were analyzed by cell type annotation, pseudotime analysis, enrichment analysis, cell interactions, single-cell regulatory network inference and clustering (SCENIC) for each cell type.
A total of 87,542 cells were analyzed and divided into 9 clusters. Six chondrocyte subpopulations were finally identified by cellular annotation, and two new chondrocyte subtypes were annotated as immune-associated chondrocytes. The presence of each chondrocyte subpopulation and its distribution were verified using immunohistochemical staining (IHC). In this study, the atlas of femoral cartilage in knee rheumatoid arthritis and 2 new immune-related chondrocytes were validated using scRNA-seq and IHC, and chondrocytes in the weight-bearing and non-weight-bearing regions of the femur were compared. There might be a process of macrophage polarization transition in MCs in response to mechanical loading, as in macrophages.
Two new immune-associated chondrocytes were identified. MCs have contrasting functions in different regions, which might provide insight into the role of immune and mechanical loading on chondrocytes in the development of knee rheumatoid osteoarthritis.
类风湿关节炎（RA）是一种常见的自身免疫性关节疾病，其发病机制尚不清楚。软骨损伤是该病的主要表现之一。软骨细胞是关节软骨的主要功能成分，与疾病进展有关。机械负荷会影响关节软骨和软骨细胞的结构和功能，但关于 RA 中负重对软骨细胞的影响尚不清楚。
本文对取自股骨负重区（Fb 组）和非负重区（Fnb 组）的软骨进行了单细胞 RNA 测序（scRNA-seq），通过细胞类型注释、拟时分析、富集分析、细胞相互作用、单细胞调控网络推断和聚类（SCENIC）对 Fb 和 Fnb 组之间的差异进行了分析。
共分析了 87542 个细胞，并分为 9 个簇。通过细胞注释最终确定了 6 个软骨细胞亚群，并注释了 2 个新的与免疫相关的软骨细胞亚型。通过免疫组织化学染色（IHC）验证了每个软骨细胞亚群的存在及其分布。本研究利用 scRNA-seq 和 IHC 验证了膝关节类风湿关节炎股骨软骨图谱和 2 个新的免疫相关软骨细胞，并比较了股骨负重区和非负重区的软骨细胞。在机械负荷作用下，MC 中可能存在巨噬细胞极化转换的过程，与巨噬细胞类似。
鉴定出了 2 种新的与免疫相关的软骨细胞。MC 在不同区域具有相反的功能，这可能为免疫和机械负荷对膝类风湿关节炎软骨细胞的作用提供新的认识。
