Epimedin C alleviated osteoarthritis development by regulating chondrocyte Nrf2-mediated NLRP3 inflammasome axis

Osteoarthritis (OA) is a prevalent musculoskeletal disorder globally. This study explored the therapeutic potential of Epimedin C (Epi C) in OA and its mechanisms. We isolated primary chondrocytes from mice and induced inflammatory damage using interleukin-1β (IL-1β) to evaluate Epi C's capacit...

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Bibliographic Details
Main Authors: Changchang Liu, Guangyu Duan, Shengjie Xu, Teng Li, Xin Sun
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Heliyon
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Online Access:http://www.sciencedirect.com/science/article/pii/S2405844024164894
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Summary:Osteoarthritis (OA) is a prevalent musculoskeletal disorder globally. This study explored the therapeutic potential of Epimedin C (Epi C) in OA and its mechanisms. We isolated primary chondrocytes from mice and induced inflammatory damage using interleukin-1β (IL-1β) to evaluate Epi C's capacity to preserve cell viability and inhibit apoptosis, employing cell counting kit (CCK8) assays, EdU staining, and flow cytometry. Additionally, its anti-inflammatory effects were quantified using enzyme-linked immunosorbent assay (ELISA), Western blot, and real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), alongside assessments of extracellular matrix (ECM) degradation. In vivo, OA was induced in mice through destabilization of the medial meniscus (DMM), followed by Epi C administration. Cartilage integrity was evaluated via micro-computed tomography (CT) and histology. Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway involvement was investigated through siRNA knockdown and oxidative stress markers, while NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome expression was measured to establish Epi C's modulatory effect. Our study revealed that Epi C protected against IL-1β-induced chondrocyte damage by enhancing cell viability, reducing apoptosis, and dampening inflammatory responses. The in vivo studies demonstrated Epi C's role in preserving cartilage structure, activating nuclear factor erythroid 2-related factor 2 (Nrf2), and inhibiting NLRP3 expression in DMM-induced OA mice. Conclusively, our findings provide substantial evidence of Epi C's therapeutic efficacy in OA, primarily through its modulation of the Nrf2-mediated NLRP3 inflammasome pathway, offering novel insights into its management role in OA.
ISSN:2405-8440