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image of Expression of miR-92a in Green Tea EGCG Preconditioned Adipose-derived Stem Cells Ameliorates Inflammatory Response and Increases Cartilage Regeneration in RA Rats through KLF4/IL-17/MMP-2 Axis Modulation

Abstract

Background

The global prevalence of rheumatoid arthritis (RA) is on the rise. Numerous studies have demonstrated the potential of stem cell-based therapies in RA treatment. Experimental evidence suggests that preconditioning enhances the regenerative capabilities of stem cells compared to their unconditioned counterparts.

Objective

This study aimed to evaluate whether adipose-derived stem cells (ADSCs) preconditioned with green tea epigallocatechin gallate (EGCG) and miR-92a exhibit superior therapeutic effects in RA compared to unconditioned ADSCs.

Methods

Both and models were employed. In the cellular model, ADSCs were preconditioned with EGCG and miR-92a. In the animal model, male Wistar rats were used, and RA was induced using the collagen-induced arthritis (CIA) model. Following RA induction, the animals were divided into six groups: Sham (healthy rats), RA (RA-induced rats), RA+ADSC (RA-induced rats receiving unconditioned ADSCs), RA+E-ADSC (RA-induced rats receiving EGCG-preconditioned ADSCs), RA+mic-ADSC (RA-induced rats receiving miR-92a mimic-preconditioned ADSCs), and RA+inh-ADSC (RA-induced rats receiving miR-92a inhibitor-preconditioned ADSCs).

Results

In the cellular model, preconditioning with EGCG and miR-92a activated the CXCR4/p-Akt signaling pathway, thereby enhancing ADSC viability. In the animal model, RA induction caused several joint pathologies, including hind paw swelling, disrupted bone metabolism, immune cell infiltration, increased expression of IL-17, KLF4, and IL-6, as well as cartilage degradation. While transplantation of unconditioned ADSCs modestly improved these pathological features, the administration of E-ADSCs and mic-ADSCs significantly ameliorated these conditions in RA rats. Conversely, the therapeutic effects of E-ADSCs and mic-ADSCs were attenuated by the transplantation of inh-ADSCs.

Conclusion

The therapeutic effects of E-ADSCs and mic-ADSCs in RA were strongly associated with the modulation of the KLF4/IL-17/MMP-2 axis. These findings suggest that ADSCs preconditioned with EGCG and miR-92a hold considerable clinical promise for the treatment of RA.

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2025-04-03
2025-09-13

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Expression of miR-92a in Green Tea EGCG Preconditioned Adipose-derived Stem Cells Ameliorates Inflammatory Response and Increases Cartilage Regeneration in RA Rats through KLF4/IL-17/MMP-2 Axis Modulation
Bentham Science Publishers ; https://doi.org/10.2174/0115665232339721250313075146
/content/journals/cgt/10.2174/0115665232339721250313075146
/content/journals/cgt/10.2174/0115665232339721250313075146
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  • Article Type:     Research Article
Keywords: mic-ADSCs ; mesenchymal stem cell ; green tea EGCG ; Rheumatoid arthritis ; miR-92a ; preconditioning

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