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 su...

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Main Authors: Wu Xiao-dong, Liang You-bang, Niu Yun-bao, Yang Yi-hong, Huang Wen-zhi, Wang Mao-jie, Mei Li-yan, Gao Kai-xin, Huang Run-yue, Chen Xiu-min
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Biological Research
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Online Access:https://doi.org/10.1186/s40659-025-00628-z
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Summary: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.
ISSN:0717-6287