Jiang Chao, Gong Yuhang, Wu Xinyu, Chen Jiangjie, Chen Yiyu, Chen Jingyao, Tang Fang, Fang Zhiyu, Bao Yuxuan, Ye Jiajing, Wang Zhangfu, Hong Zhenghua
Department of Orthopaedics, Taizhou Hospital Affiliated to Wenzhou Medical University, Taizhou, China.
Enze Medical Research Center, Taizhou Hospital Affiliated to Wenzhou Medical University, Taizhou, China.
J Orthop Translat. 2025 Apr 25;52:220-232. doi: 10.1016/j.jot.2025.04.008. eCollection 2025 May.
Osteoarthritis (OA), the most prevalent form of arthritis, is swiftly emerging as a chronic health condition, that poses the primary cause of disability and significant socioeconomic burden. Despite its prevalence, effective therapeutic options for OA remain elusive. This study seeks to explore the therapeutic potential of edaravone (EDA), a FDA-approved free radical scavenger, in the context of OA development and to elucidate its underlying mechanisms.
, oxidative stress models were induced by stimulating chondrocytes with t-butylhydroperoxide (TBHP); then, we investigated the influence of EDA on chondrocyte dysfunction, apoptosis, inflammatory responses and mitochondrial function in TBHP-treated chondrocytes, along with the underlying mechanisms. , destabilization of the medial meniscus (DMM) model was used to investigate the impact of EDA on OA progression. mice were applied to determine the potential role of NRF2 as a target for EDA.
EDA notably alleviates chondrocyte dysfunction triggered by oxidative stress, safeguards chondrocytes from apoptosis and inflammatory responses, and preserves mitochondrial function and redox balance within chondrocytes. At the molecular level, EDA appears to halt the progression of OA by engaging and activating the nuclear factor erythroid 2-related factor 2 (NRF2) pathway, which is crucial for maintaining mitochondrial function and redox equilibrium. Notably, the protective effects of EDA on OA are abolished in mice, underscoring the significance of the NRF2 signaling pathway in mediating EDA's therapeutic effects.
EDA has the potential to mitigate chondrocyte degeneration, thereby slowing the progression of OA. Thus, EDA may represent a novel therapeutic agent for the treatment of OA, potentially expanding its clinical utility.
As a clinically licensed drug used for the treatment of neurological disorders, edaravone has shown promising therapeutic effects on OA development. Mechanistically, edaravone stabilized mitochondrial function and maintained redox homeostasis by activating NRF2 signaling pathway. The protective effects of edaravone against OA were verified and . These findings presented robust evidence for repurposing edaravone for the treatment of OA in clinic.
骨关节炎（OA）是最常见的关节炎形式，正迅速成为一种慢性健康问题，是导致残疾的主要原因和重大社会经济负担。尽管其发病率很高，但OA的有效治疗选择仍然难以捉摸。本研究旨在探讨依达拉奉（EDA）（一种经美国食品药品监督管理局批准的自由基清除剂）在OA发展过程中的治疗潜力，并阐明其潜在机制。
通过用叔丁基过氧化氢（TBHP）刺激软骨细胞诱导氧化应激模型；然后，我们研究了EDA对TBHP处理的软骨细胞中软骨细胞功能障碍、凋亡、炎症反应和线粒体功能的影响及其潜在机制。使用内侧半月板不稳定（DMM）模型研究EDA对OA进展的影响。使用Nrf2基因敲除小鼠来确定NRF2作为EDA靶点的潜在作用。
EDA显著减轻氧化应激引发的软骨细胞功能障碍，保护软骨细胞免受凋亡和炎症反应，并维持软骨细胞内的线粒体功能和氧化还原平衡。在分子水平上，EDA似乎通过参与并激活核因子红细胞2相关因子2（NRF2）途径来阻止OA的进展，该途径对于维持线粒体功能和氧化还原平衡至关重要。值得注意的是，在Nrf2基因敲除小鼠中，EDA对OA的保护作用被消除，这突出了NRF2信号通路在介导EDA治疗作用中的重要性。
EDA有减轻软骨细胞退变的潜力，从而减缓OA的进展。因此，EDA可能代表一种治疗OA的新型治疗药物，可能扩大其临床应用。
作为一种用于治疗神经系统疾病的临床许可药物，依达拉奉已显示出对OA发展有良好的治疗效果。从机制上讲，依达拉奉通过激活NRF2信号通路稳定线粒体功能并维持氧化还原稳态。依达拉奉对OA的保护作用在细胞实验和动物实验中得到了验证。这些发现为依达拉奉在临床上重新用于治疗OA提供了有力证据。
