Department of Orthopedics, Renmin Hospital of Wuhan University, No. 99 Zhangzhidong Road, Wuchang District, Wuhan, 430060, China.
Department of Orthopedics, Renmin Hospital of Wuhan University, No. 99 Zhangzhidong Road, Wuchang District, Wuhan, 430060, China.
Food Chem Toxicol. 2023 Apr;174:113644. doi: 10.1016/j.fct.2023.113644. Epub 2023 Jan 31.
Osteoarthritis (OA) is a common degenerative joint disease, mainly presented by the deterioration of articular cartilage. Amounts of data demonstrated this deterioration is composed of oxidative stress, pro-inflammation and chondrocyte death events. Ferroptosis is a novel form of cell death that differs from apoptosis and autophagy, recent studies have shown that chondrocyte ferroptosis contributes to the development of osteoarthritis. Cardamonin (CAD) has been demonstrated to possess antioxidant and anti-inflammatory properties in several diseases, whether CAD may influence the OA progression is still obscure. Therefore, we aimed to determine whether CAD alleviates chondrocyte ferroptosis and its effect on OA with potential mechanism. In this study, we found that inflammation, cartilage degradation and ferroptosis induced by interleukin-1β (IL-1β) were significantly alleviated by CAD. Moreover, the administration of the ferroptosis inhibitor, Deferoxamine (DFO) reversed the inflammatory and cartilage degradation effects of IL-1β as well. Chondrocyte mitochondrial morphology and function were alleviated by both CAD and DFO. We found that CAD increased collagen II, p53, SLC7A11 GPX4 expression and decreased MMP13, iNOS, COX2 expression in chondrocytes, further investigation showed that the P53 signaling pathway was involved. In vivo, intra-articular injection of CAD significantly ameliorated cartilage damage in a rat OA model, induced collagen II and SLC7A11 expression by immunohistochemistry. Our study proves that CAD ameliorated OA cartilage degradation by regulating ferroptosis via P53 signaling pathway, suggesting a potential role of CAD in OA treatment.
骨关节炎（OA）是一种常见的退行性关节疾病，主要表现为关节软骨的恶化。大量数据表明，这种恶化是由氧化应激、促炎和软骨细胞死亡事件组成的。铁死亡是一种新型的细胞死亡形式，与细胞凋亡和自噬不同，最近的研究表明，软骨细胞铁死亡有助于骨关节炎的发展。小豆蔻明（CAD）已被证明在多种疾病中具有抗氧化和抗炎作用，CAD 是否会影响 OA 的进展尚不清楚。因此，我们旨在确定 CAD 是否可以减轻软骨细胞铁死亡并通过潜在机制影响 OA。在这项研究中，我们发现 CAD 显著减轻了白细胞介素 1β（IL-1β）诱导的炎症、软骨降解和铁死亡。此外，铁死亡抑制剂去铁胺（DFO）的给药也逆转了 IL-1β 的炎症和软骨降解作用。CAD 和 DFO 均可减轻软骨细胞的线粒体形态和功能。我们发现 CAD 增加了软骨细胞中的胶原蛋白 II、p53、SLC7A11 GPX4 的表达，降低了 MMP13、iNOS、COX2 的表达，进一步的研究表明 P53 信号通路参与其中。在体内，关节内注射 CAD 可显著改善大鼠 OA 模型中的软骨损伤，通过免疫组织化学诱导胶原蛋白 II 和 SLC7A11 的表达。我们的研究证明，CAD 通过 P53 信号通路调节铁死亡来改善 OA 软骨降解，提示 CAD 在 OA 治疗中的潜在作用。
