Miyahara Junya, Omata Yasunori, Chijimatsu Ryota, Okada Hiroyuki, Ishikura Hisatoshi, Higuchi Junya, Tachibana Naohiro, Nagata Kosei, Tani Shoichiro, Kono Kenichi, Kawaguchi Kohei, Yamagami Ryota, Inui Hiroshi, Taketomi Shuji, Iwanaga Yasuhide, Terashima Asuka, Yano Fumiko, Seki Masahide, Suzuki Yutaka, Baron Roland, Tanaka Sakae, Saito Taku
Sensory & Motor System Medicine.
Bone and Cartilage Regenerative Medicine.
JCI Insight. 2025 Jan 23;10(2):e183690. doi: 10.1172/jci.insight.183690.
Osteoarthritis (OA) shows various clinical manifestations depending on the status of its joint components. We aimed to identify the synovial cell subsets responsible for OA pathophysiology by comprehensive analyses of human synovium samples in single-cell resolution. Two distinct OA synovial tissue groups were classified by gene expression profiles in RNA-Seq: inflammatory and fibrotic. The inflammatory group exhibited high expression of inflammatory cytokines, histologically inflammatory infiltrate, and a more severe pain score. The fibrotic group showed higher expression of fibroblast growth factor (FGFs) and bone morphogenetic proteins (BMPs), showed histologically perivascular fibrosis, and showed a lower pain score. In single-cell RNA-Seq (scRNA-Seq) of synovial cells, MERTKloCD206lo macrophages and CD34hi fibroblasts were associated with the inflammatory and fibrotic groups, respectively. Among the 3 fibroblast subsets, CD34loTHY1lo and CD34loTHY1hi fibroblasts were influenced by synovial immune cells, whereas CD34hi fibroblasts were influenced by mural and endothelial cells. Particularly, in CD34hi fibroblast subsets, CD34hiCD70hi fibroblasts promoted proliferation of Tregs, potentially suppressing synovitis and protecting articular cartilage. Elucidation of the mechanisms underlying the regulation of these synovial cell subsets may lead to novel strategies for OA therapeutics.
骨关节炎（OA）根据其关节组成部分的状况表现出各种临床表现。我们旨在通过对人类滑膜样本进行单细胞分辨率的综合分析，确定负责OA病理生理学的滑膜细胞亚群。通过RNA测序中的基因表达谱将两种不同的OA滑膜组织组进行了分类：炎症性和纤维化。炎症组表现出炎症细胞因子的高表达、组织学上的炎症浸润以及更严重的疼痛评分。纤维化组显示成纤维细胞生长因子（FGFs）和骨形态发生蛋白（BMPs）的表达更高，组织学上显示血管周围纤维化，且疼痛评分较低。在滑膜细胞的单细胞RNA测序（scRNA-Seq）中，MERTKloCD206lo巨噬细胞和CD34hi成纤维细胞分别与炎症组和纤维化组相关。在3个成纤维细胞亚群中，CD34loTHY1lo和成纤维细胞CD34loTHY1hi受滑膜免疫细胞影响，而CD34hi成纤维细胞受壁细胞和内皮细胞影响。特别地，在CD34hi成纤维细胞亚群中，CD34hiCD70hi成纤维细胞促进调节性T细胞（Tregs）的增殖，可能抑制滑膜炎并保护关节软骨。阐明这些滑膜细胞亚群的调节机制可能会带来OA治疗的新策略。
