Exosomes derived from fibrinogen-like protein 1-overexpressing bone marrow-derived mesenchymal stem cells ameliorates rheumatoid arthritis

Abstract

ABSTRACT 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.