Quercetin-primed MSC exosomes synergistically attenuate osteoarthritis progression

Abstract Background Osteoarthritis (OA), a degenerative joint disease characterized by cartilage degradation and inflammation, lacks effective disease-modifying therapies. Quercetin, a bioactive flavonoid derived from Traditional Chinese Medicine, exhibits anti-inflammatory and chondroprotective pro...

Full description

Saved in:
Bibliographic Details
Main Authors: Mingfeng Lu, Aiju Lou, Junqing Gao, Shilin Li, Lilei He, Weifeng Fan, Lilian Zhao
Format: Article
Language:English
Published: BMC 2025-04-01
Series:Journal of Orthopaedic Surgery and Research
Subjects:
Online Access:https://doi.org/10.1186/s13018-025-05785-1
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Background Osteoarthritis (OA), a degenerative joint disease characterized by cartilage degradation and inflammation, lacks effective disease-modifying therapies. Quercetin, a bioactive flavonoid derived from Traditional Chinese Medicine, exhibits anti-inflammatory and chondroprotective properties but is limited by poor bioavailability. Mesenchymal stem cell-derived exosomes (MSC-Exos) offer a promising strategy for targeted drug delivery and cartilage regeneration. Methods Bone marrow-derived MSC exosomes (Que-Exo) were isolated after preconditioning with quercetin (1µM, 24 h). Their effects were evaluated in IL-1β-stimulated chondrocytes via RT-qPCR, Western blot, transcriptomics, and proteomics. An ACLT-induced OA mouse model received intra-articular injections of Que-Exo, with cartilage integrity assessed by Safranin O staining and OARSI scoring. Results Que-Exo significantly reduced IL-1β-induced pro-inflammatory markers (MMP9 and COX-2) and restored cartilage repair genes (SOX9 and Collagen II) compared to untreated exosomes. Multi-omics analyses revealed activation of PI3K-AKT signaling and glutathione metabolism pathways. In vivo, Que-Exo mitigated cartilage degradation and preserved proteoglycan content. Conclusions Quercetin-preconditioned MSC exosomes synergistically enhance chondroprotection and anti-inflammatory effects, offering a novel therapeutic strategy for OA by combining herbal bioactive compounds with exosome-mediated delivery.
ISSN:1749-799X