Department of Orthopaedics, the Affiliated Laishan Branch of Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China.
Department of Traumatic Orthopaedics, the Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China.
Bioengineered. 2022 Jun;13(6):14545-14561. doi: 10.1080/21655979.2022.2090379.
Rheumatoid arthritis (RA) is a most common chronic joint disease belonging to inflammatory autoimmune disease. The aim of this study was to determine the role and mechanism of bone marrow mesenchymal stem cells (BMSCs)-derived exosomes and fibrinogen-like protein 1 (FGL1) overexpression exosomes shuttled by BMSCs (FGL1-Exos) on RA. All of the exosomes were visualized by transmission electron microscope (TEM) and the characteristic proteins were detected by western blot. To investigate the therapeutic effect of FGL1-Exos, RA-FLSs were activated by TNF-α and RA rat model was established by collagen incomplete Freund's adjuvant. Cell viability, apoptosis, inflammation factors, and protein levels were detected by CCK-8, flow cytometry, enzyme-linked immunosorbent assay and western blot, respectively. Hematoxylin and eosin and safranin O staining were used to detect the histopathology changes. Cell apoptosis and FGL1 expression in knee joint were detected by immunofluorescence. The results showed that FGL1-Exos could inhibit the cell viability meanwhile increase the cell apoptosis in RA-FLSs. Meanwhile, FGL1-Exos could effectively suppress the inflammation score, joint destruction, and inflammatory response in RA rat model. FGL1-Exos directly inhibited cell apoptosis of RA-FLSs and RA rat model by suppressing the inflammatory cytokines, specific rheumatoid markers, immunological markers meanwhile meditating the NF-κB pathway. Our results indicate that FGL1 was a therapeutic potential target in RA therapy.
类风湿关节炎（RA）是一种最常见的慢性关节疾病，属于炎症性自身免疫性疾病。本研究旨在确定骨髓间充质干细胞（BMSCs）衍生的外泌体和纤维蛋白原样蛋白 1（FGL1）过表达外泌体通过 BMSCs 转运（FGL1-Exos）在 RA 中的作用和机制。所有的外泌体都通过透射电子显微镜（TEM）观察到，并通过 Western blot 检测到特征蛋白。为了研究 FGL1-Exos 的治疗效果，用 TNF-α激活 RA-FLSs，用不完全弗氏佐剂胶原建立 RA 大鼠模型。通过 CCK-8、流式细胞术、酶联免疫吸附试验和 Western blot 分别检测细胞活力、细胞凋亡、炎症因子和蛋白水平。用苏木精和伊红及番红 O 染色检测组织病理学变化。通过免疫荧光检测膝关节细胞凋亡和 FGL1 表达。结果表明，FGL1-Exos 可抑制 RA-FLSs 的细胞活力，同时增加细胞凋亡。同时，FGL1-Exos 可有效抑制 RA 大鼠模型的炎症评分、关节破坏和炎症反应。FGL1-Exos 通过抑制炎症细胞因子、特异性类风湿标志物、免疫标志物，同时介导 NF-κB 通路，直接抑制 RA-FLSs 和 RA 大鼠模型的细胞凋亡。我们的结果表明，FGL1 是 RA 治疗的潜在治疗靶点。
