氧化应激
丙二醛
活性氧
脂质过氧化
医学
炎症
细胞生物学
肿瘤坏死因子α
细胞毒性
骨关节炎
药理学
分子生物学
化学
免疫学
生物化学
体外
内科学
生物
病理
替代医学
作者
Jiuxiang Liu,Hao Zhou,Jiangqi Chen,Qiang Zuo,Feng Liu
标识
DOI:10.1186/s13018-023-04483-0
摘要
Osteoarthritis (OA) is a common degenerative disease involving articular cartilage, in which ferroptosis of chondrocytes plays an important role. Baicalin (BAI) exerts regulatory effects in a wide range of orthopedic diseases including OA, but its effect on ferroptosis of chondrocytes (CHs) is still unclear. The purpose of this study was to determine the effect of BAI on ferroptosis in human OA chondrocytes (OACs), and to explore its possible mechanism.CHs were treated with IL-1β (10 ng/mL) to simulate inflammation in vitro. Immunofluorescence, quantitative RT-PCR, Western blotting and cell viability assay were performed to evaluate the impacts of BAI on Fe2+ level, mitochondrial dysfunction, ferroptosis-related proteins, oxidative stress and cytotoxicity in CHs. Additionally, siRNA was made use of to knock out nuclear factor E2-related factor 2 (Nrf2) to analyze the role played by Nrf2 in BAI-induced CH ferroptosis.BAI eliminated IL-1β-induced Fe2+ accumulation, changes in mitochondrial membrane potential and ferroptosis-related protein GPX4, SLC7A11, P53 and ACSL4 levels, as well as reactive oxygen species (ROS), lipid peroxidation (LPO) and malondialdehyde (MDA) accumulation in CHs. Besides, BAI reversed IL-1β-induced decrease of Collagen II and increase of MMP13 in CHs. Meanwhile, BAI attenuated IL-1β-induced CH toxicity and promoted Nrf2 antioxidant system activation. When Nrf2 was knocked down by siRNA, the effects of BAI on IL-1β-induced ferroptosis-related proteins and antioxidant stress in CHs were significantly weakened.This study demonstrates that IL-1β can induce CH ferroptosis. BAI is able to inhibit IL-1β-induced CH ferroptosis and ECM degradation, and the specific mechanism may be that it can inhibit IL-1β-induced CH ferroptosis by activating Nrf2 antioxidant system to attenuate the accumulation of intracellular ROS and lipid ROS.
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