Cai Dawei, Yan Huyong, Liu Jun, Chen Sichun, Jiang Longhai, Wang Xiaoxu, Qin Jian
Department of Orthopaedics, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu 211100, P.R. China.
Department of Orthopaedics, The Second Affiliated Hospital of Nanhua University, Hengyang, Hunan 421000, P.R. China.
Exp Ther Med. 2021 Mar;21(3):194. doi: 10.3892/etm.2021.9627. Epub 2021 Jan 8.
Osteoarthritis (OA) is a common joint disorder characterized by progressive articular cartilage degeneration and destruction and results in gradual disability among middle-aged and elderly patients. Our previous study demonstrated that depletion of nuclear factor erythroid 2-related factor 2 (Nrf2) exacerbated cartilage erosion in an OA model and that activation of the Nrf2 pathway could counter this process. As a downstream target of Nrf2, heme oxygenase (HO) degrades heme to free iron, biliverdin and carbon monoxide (CO), which protects against oxidative stress. Ergosterol (ER), which is extracted from fungi, is a newly discovered Nrf2 activator and displayed efficacy against myocardial injury. The present study aimed to investigate the potential protective effects of ER against cartilage damage during OA. Primary mouse chondrocytes were treated with ER for assays. Furthermore, mice that underwent destabilization of the medial meniscus surgery were orally administered with ER. Western blotting suggested that ER increased protein expression of Nrf2 and HO-1 in primary chondrocytes and articular cartilage from knee joints. Cartilage damage in knee joints was significantly reduced by ER treatment. Western blotting and PCR analysis confirmed that ER could also suppress the expression of MMP-9 and MMP-13 and . The present findings suggested that ER effectively alleviated cartilage degradation and that activation of the Nrf2-heme oxygenase 1 pathway may play a role in ER-mediated cartilage protection against OA.
骨关节炎（OA）是一种常见的关节疾病，其特征是关节软骨进行性退变和破坏，导致中老年患者逐渐残疾。我们之前的研究表明，在骨关节炎模型中，核因子红细胞2相关因子2（Nrf2）的缺失会加剧软骨侵蚀，而Nrf2途径的激活可以对抗这一过程。作为Nrf2的下游靶点，血红素加氧酶（HO）将血红素降解为游离铁、胆绿素和一氧化碳（CO），从而抵御氧化应激。从真菌中提取的麦角固醇（ER）是一种新发现的Nrf2激活剂，对心肌损伤具有疗效。本研究旨在探讨ER对骨关节炎期间软骨损伤的潜在保护作用。用ER处理原代小鼠软骨细胞进行检测。此外，对接受内侧半月板手术失稳的小鼠口服给予ER。蛋白质印迹法表明，ER增加了原代软骨细胞和膝关节软骨中Nrf2和HO-1的蛋白表达。ER处理显著减少了膝关节的软骨损伤。蛋白质印迹法和PCR分析证实，ER还可以抑制MMP-9和MMP-13的表达。本研究结果表明，ER有效减轻了软骨退变，Nrf2-血红素加氧酶1途径的激活可能在ER介导的软骨保护免受骨关节炎影响中发挥作用。
