Department of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230022, China; Graduate School, Bengbu Medical University, Bengbu 233000, China.
Department of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230022, China.
Int Immunopharmacol. 2024 Dec 25;143(Pt 1):113336. doi: 10.1016/j.intimp.2024.113336. Epub 2024 Oct 7.
Synovial inflammation, Cartilage erosion, and subchondral osteosclerosis, which are collectively referred to as the triad of pathogenesis, contribute to osteoarthritis (OA) progression. Specifically, the M1 macrophage in the synovium worsens the development of the illness and is a significant factor in the deterioration and functioning of cartilage.
To investigate whether Ruscogenin attenuates progressive degeneration of articular cartilage in rats with anterior cruciate ligament transection (ACLT)-induced osteoarthritis (OA) by modulating macrophage reprogramming and to explore its specific mechanism of action.
In vitro, SW1353 cells and RAW264.7 cells were applied to elucidate the mechanisms by which Ruscogenin protects articular cartilage. Specifically, the expression levels of molecules related to cartilage ECM synthesis and degradation enzymes and macrophages were analysed. In vivo, a rat osteoarthritis model was established using ACLT. The protective effect of Ruscogenin on articular cartilage was observed.
Ruscogenin significantly reversed LPS-induced macrophage inflammatory response and promoted cartilage regeneration-related factors. In addition, Ruscogenin had a significant protective effect on the knee joint of ACLT rats, effectively preventing cartilage degeneration. These positive therapeutic effects were achieved on the one hand by Ruscogenin regulating macrophage reprogramming by targeting Sirt3, and on the other hand Ruscogenin could attenuate the ROS level of chondrocytes thereby inhibiting chondrocyte ferroptosis.
Ruscogenin exerts chondroprotective effects by regulating macrophage reprogramming and inhibiting chondrocyte ferroptosis.
滑膜炎症、软骨侵蚀和软骨下骨硬化，统称为发病三联征，共同导致骨关节炎（OA）的进展。具体来说，滑膜中的 M1 巨噬细胞加剧了疾病的发展，是软骨恶化和功能障碍的重要因素。
通过调节巨噬细胞重编程，研究毛蕊异黄酮是否能减轻前交叉韧带切断（ACLT）诱导的骨关节炎（OA）大鼠关节软骨的进行性退变，并探讨其具体作用机制。
在体外，应用 SW1353 细胞和 RAW264.7 细胞阐明毛蕊异黄酮保护关节软骨的机制。具体来说，分析与软骨 ECM 合成和降解酶以及巨噬细胞相关的分子的表达水平。在体内，采用 ACLT 建立大鼠骨关节炎模型。观察毛蕊异黄酮对关节软骨的保护作用。
毛蕊异黄酮能显著逆转 LPS 诱导的巨噬细胞炎症反应，促进软骨再生相关因子。此外，毛蕊异黄酮对 ACLT 大鼠的膝关节有显著的保护作用，能有效防止软骨退化。这些积极的治疗效果一方面是通过毛蕊异黄酮通过靶向 Sirt3 调节巨噬细胞重编程实现的，另一方面毛蕊异黄酮可以降低软骨细胞的 ROS 水平，从而抑制软骨细胞铁死亡。
毛蕊异黄酮通过调节巨噬细胞重编程和抑制软骨细胞铁死亡发挥软骨保护作用。
