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Background <p>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.</p> Methods <p>Bone marrow-derived MSC exosomes (Que-Exo) were isolated after preconditioning with quercetin (1µM, 24&#xa0;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.</p> Results <p>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.</p> Conclusions <p>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.</p>

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Quercetin-primed MSC exosomes synergistically attenuate osteoarthritis progression

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月15日

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  • Mingfeng Lu,
  • Aiju Lou,
  • Junqing Gao,
  • Shilin Li,
  • Lilei He,
  • Weifeng Fan,
  • Lilian Zhao

摘要

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.