骨关节炎
软骨细胞
活性氧
软骨
炎症
氧化应激
化学
细胞生物学
药理学
体外
分子生物学
生物
免疫学
生物化学
病理
医学
解剖
替代医学
作者
Hongjie Chen,Yiming Zhong,Weilin Sang,Cong Wang,Haiming Lu,Lai Peng,Libo Zhu,Jinzhong Ma
标识
DOI:10.1016/j.bbrc.2024.149599
摘要
Osteoarthritis is highly prevalent joint disease; however, effective treatments are lacking. Protopine (PTP) is an isoquinoline alkaloid with potent anti-inflammatory and antioxidant properties; however, it has not been studied in osteoarthritis. This study aimed to investigate whether PTP can effectively protect chondrocytes from ferroptosis. To the end, primary mouse chondrocytes were treated with tert-butyl hydroperoxide (TBHP) to simulate oxidative stress in an in vitro model of osteoarthritis. Two concentrations of PTP (10 and 20 μg/mL) were validated for in vitro experiments. Cellular inflammation and metabolism were detected using RT-qPCR and western blotting (WB). Ferroptosis was assessed via WB, qPCR, reactive oxygen species (ROS) levels, lipid ROS, and immunofluorescence staining. In vitro, PTP significantly ameliorated chondrocyte inflammation and cytolytic metabolism and significantly suppressed chondrocyte ferroptosis through the activation of the Nrf2 pathway. The anterior cruciate ligament transection (ACLT) mouse model was used to validate the in vivo effects of PTP. The joint cartilage was assessed using the Osteoarthritis Research Society International (OARSI) score, Safranin O staining, and immunohistochemistry. The intra-articular administration of PTP alleviated cartilage inflammation and ferroptosis, as evidenced by the expression of MMP3, MMP13, COL2A1, GPX4, and Nrf2. Overall, we found that PTP exerts anti-ferroptosis and anti-inflammatory effects on chondrocytes to protect the articular cartilage.
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