Ginsenoside Rh2-Pretreated Mesenchymal Stem Cell Exosomes Ameliorate Collagen-Induced Arthritis via N6-Methyladenosine Methylation.

Abstract

This research examines the impact of exosomes derived from mesenchymal stem cells that have been pretreated with ginsenoside Rh2 (Rh2-pre Exo) in the context of collagen-induced arthritis (CIA). Rheumatoid arthritis (RA) is a persistent inflammatory condition marked by joint pain and swelling, which, in advanced stages, may result in joint damage and reduced functionality. We found that Rh2-pro Exo regulates the Toll-like receptor 4 (TLR4)/Myd88/nuclear factor κB (NF-κB) signaling pathway by modulating the m6A methylation levels of C-C motif chemokine receptor like 2 (CCRL2). The interaction between CCRL2 and TLR4 is a key factor influencing the activity of this signaling pathway. Our results indicate that this regulatory mechanism enhances the anti-inflammatory phenotype of macrophages, promoting a shift from pro-inflammatory to anti-inflammatory responses. Furthermore, treatment with Rh2-pre Exo substantially alleviated clinical symptoms and reduced joint damage in CIA models. These findings provide new insights into the therapeutic potential of Rh2-pre Exo in the treatment of RA, emphasizing the importance of m6A methylation in regulating immune responses. This study suggests that targeting the m6A methylation pathway of CCRL2 could offer a promising strategy for developing effective therapies for RA, ultimately improving patient outcomes and quality of life.