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槲皮素预处理的间充质干细胞外泌体协同减轻骨关节炎进展。

Quercetin-primed MSC exosomes synergistically attenuate osteoarthritis progression.

作者信息

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

机构信息

The Eighth Clinical Medical College of Guangzhou University of Chinese Medicine, Foshan, Guangdong, 528000, China.

Foshan Hospital of Traditional Chinese Medicine, Foshan, Guangdong, 528000, China.

出版信息

J Orthop Surg Res. 2025 Apr 15;20(1):373. doi: 10.1186/s13018-025-05785-1.

DOI:10.1186/s13018-025-05785-1
PMID:40229791
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11998445/
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.

摘要

背景

骨关节炎（OA）是一种以软骨降解和炎症为特征的退行性关节疾病，缺乏有效的疾病修饰疗法。槲皮素是一种源自中药的生物活性黄酮类化合物，具有抗炎和软骨保护特性，但生物利用度较差。间充质干细胞衍生的外泌体（MSC-Exos）为靶向药物递送和软骨再生提供了一种有前景的策略。

方法

用槲皮素（1µM，24小时）预处理后分离骨髓来源的MSC外泌体（Que-Exo）。通过RT-qPCR、蛋白质印迹、转录组学和蛋白质组学在白细胞介素-1β刺激的软骨细胞中评估其作用。前交叉韧带切断术诱导的OA小鼠模型接受关节内注射Que-Exo，通过番红O染色和OARSI评分评估软骨完整性。

结果

与未处理的外泌体相比，Que-Exo显著降低白细胞介素-1β诱导的促炎标志物（MMP9和COX-2），并恢复软骨修复基因（SOX9和胶原蛋白II）。多组学分析揭示了PI3K-AKT信号通路和谷胱甘肽代谢途径的激活。在体内，Que-Exo减轻了软骨降解并保留了蛋白聚糖含量。

结论

槲皮素预处理的MSC外泌体协同增强软骨保护和抗炎作用，通过将草药生物活性化合物与外泌体介导的递送相结合，为OA提供了一种新疗法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c926/11998445/d6f1df64b980/13018_2025_5785_Fig7_HTML.jpg
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Osteoarthritis year in review 2024: Epidemiology and therapy.2024 年骨关节炎年度回顾：流行病学和治疗。
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