Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Korea.
Department of Family Medicine, Seoul National University Hospital, Seoul 03080, Korea.
Cells. 2021 Jan 10;10(1):120. doi: 10.3390/cells10010120.
This study aimed to investigate the characteristics of exosomes isolated from synovial fluid and their role in osteoclast differentiation in different types of inflammatory arthritis. Exosomes isolated from synovial fluid of rheumatoid arthritis (RA), ankylosing spondylitis (AS), gout, and osteoarthritis (OA) patients were co-incubated with CD14+ mononuclear cells from healthy donors without macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-B ligand (RANKL). Osteoclast differentiation was evaluated via tartrate-resistant acid phosphatase (TRAP) staining and activity and F-actin ring formation. RANKL expression on synovial exosomes was assessed using flow cytometry and an enzyme-linked immunosorbent assay (ELISA). Synovial exosomes were the lowest in OA patients; these induced osteoclastogenesis in the absence of M-CSF and RANKL. Osteoclastogenesis was significantly higher with more exosomes in RA ( = 0.030) than in OA patients, but not in AS or gout patients. On treating macrophages with a specified number of synovial exosomes from RA/AS patients, exosomes induced greater osteoclastogenesis in RA than in AS patients. Synovial exosomal RANKL levels were significantly higher in RA ( = 0.035) than in AS patients. Synovial exosome numbers vary with the type of inflammatory arthritis. Synovial exosomes from RA patients may bear the disease-specific "synovial signature of osteoclastogenesis."
本研究旨在探讨关节滑液来源的外泌体的特征及其在不同类型炎症性关节炎中破骨细胞分化中的作用。将类风湿关节炎 (RA)、强直性脊柱炎 (AS)、痛风和骨关节炎 (OA) 患者关节滑液中分离的外泌体与未添加巨噬细胞集落刺激因子 (M-CSF) 和核因子 kappa-B 配体受体激活剂 (RANKL) 的健康供体 CD14+单核细胞共孵育。通过抗酒石酸酸性磷酸酶 (TRAP) 染色和活性以及 F-肌动蛋白环形成来评估破骨细胞分化。使用流式细胞术和酶联免疫吸附试验 (ELISA) 评估滑膜外泌体上的 RANKL 表达。OA 患者的滑膜外泌体最低；这些外泌体在没有 M-CSF 和 RANKL 的情况下诱导破骨细胞生成。RA 患者的破骨细胞生成率显著高于 OA 患者（=0.030），但 AS 或痛风患者则不然。用 RA/AS 患者的特定数量的滑膜外泌体处理巨噬细胞后，RA 患者的外泌体诱导的破骨细胞生成率高于 AS 患者。RA 患者的滑膜外泌体 RANKL 水平明显高于 AS 患者（=0.035）。滑膜外泌体数量随炎症性关节炎的类型而异。RA 患者的滑膜外泌体可能具有疾病特异性的“破骨细胞生成滑膜特征”。
