Chinese herbal formula Huayu-Qiangshen-Tongbi decoction ameliorates rheumatoid arthritis through enhancing the release of exosomal miR-125b-5p derived from adipose-derived stem cells by CD63.

Abstract

Background: Rheumatoid arthritis (RA) is a chronic and multifactorial inflammatory disease inducing damages in joints and extra-articular organs. Our previous study has revealed that Huayu-Qiangshen-Tongbi decoction (HQT) ameliorates RA through upregulating microRNA (miRNA) miR-125b-5p to suppress inflammation in rheumatoid fibroblast-like synoviocytes (FLSs). However, the mechanism of HQT increasing miR-125b-5p level in FLSs remains unclear. It has been reported that exosomal miR-125b-5p derived from adipose-derived stem cells (ADSCs) could ameliorate various diseases, yet the effect of exosomal miR-125b-5p derived from ADSCs on FLSs in RA under HQT treatment is largely unknown. The aim is to investigate whether HQT upregulated miR-125b-5p in FLSs through modifying exosomal miR-125b-5p derived from ASCs.

Methods: Here, HQT-containing serum was prepared, co-culture of human FLS MH7A cells with ADSCs was performed, gene knockdown in ADSCs was assessed by short hairpin RNA (shRNA), protein degradation was identified after cycloheximide (CHX) treatment and ADSC-derived exosomes were collected to incubate MH7A cells and inject into RA rat model.

Results: HQT elevates lipopolysaccharide (LPS)-reduced miR-125b-5p level in FLSs by enhancing the secretion of exosomal miR-125b-5p derived from ADSCs. Besides, HQT attenuates inflammation of FLSs in RA by exosomal miR-125b-5p derived from ADSCs in vitro and in vivo. Mechanistically, HQT suppresses CD63 degradation in ADSCs to facilitate the release of exosomal miR-125b-5p derived from ADSCs.

Conclusion: In summary, these findings reveal the mechanism of HQT elevating miR-125b-5p expression in FLSs and provide novel therapeutic strategy for RA treatment.