Rheumatoid arthritis (RA) is a chronic autoimmune disease closely correlated to synovial tissue inflammation. Exosomes are known to transfer microRNAs (miRNAs) between cells and have been validated as the vehicles for delivery of therapeutic molecules.
The current study was set to examine the functional values of bone marrow-derived mesenchymal stem cells (BMSCs)-secreted exosomal miR-192-5p (exo-miR-192-5p) on inflammation in RA.
Following the screening of differentially expressed genes in RA and miRNA-mRNA target prediction, BMSCs were infected with lentivirus expressing miR-192-5p to obtain miR-192-5p-overexpressed exosomes. To study the effect of exo-miR-192-5p on the expression of ras-related C3 botulinum toxin substrate 2 (RAC2), collagen-induced arthritis (CIA) rat models were established, and the clinical and histopathological changes were evaluated in the rats injected with exosomes. Subsequently, the expression patterns of pro-inflammatory factors were determined by ELISA.
miR-192-5p was found to be down-regulated, while RAC2 was up-regulated in RA samples. Bioinformatics prediction revealed that the up-regulated RAC2 in RA may be regulated by miR-192-5p, which was further confirmed by dual luciferase reporter gene assay. The clinical arthritic scores, joint destruction, and inflammatory response were reduced after the injection of exosomes in rats with CIA targeting RAC2, and the treatment efficacy was even better with miR-192-5p-overexpressed exosomes.
Our study established that the BMSCs-secreted exosomal miR-192-5p can delay the event of the inflammatory response in RA and may represent a possible therapeutic strategy for the treatment of RA.