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...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-04-01
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| Series: | Journal of Orthopaedic Surgery and Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13018-025-05785-1 |
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| 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. |
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| ISSN: | 1749-799X |