HMGB1
下调和上调
骨关节炎
水通道蛋白
氧化应激
医学
软骨
水通道蛋白4
水肿
转录组
软骨细胞
药理学
癌症研究
病理
内科学
生物
炎症
基因表达
生物化学
解剖
生理学
基因
替代医学
作者
Yudong Liu,Tengteng Xu,Zhaochen Ma,Zhaowei Chu,Mingzhu Xu,Qun Li,Weiheng Chen,Yanqiong Zhang,Chunfang Liu,Na Lin
出处
期刊:Phytomedicine
[Elsevier]
日期:2024-07-01
卷期号:129: 155593-155593
标识
DOI:10.1016/j.phymed.2024.155593
摘要
Preventing joint edema is crucial in halting osteoarthritis (OA) progression. Growing clinical evidence indicate that Jianpi-Tongluo Formula (JTF) may have a promising anti-edema effect. However, the therapeutic properties of JTF and the underlying mechanisms remains unclear. An OA rat model was established and employed to evaluate pharmacological effects of JTF in vivo based on dynamic histopathologic assessments and micro-CT observations. Then, OA-related genes and potential targets of JTF were identified through clinical transcriptomic data analysis and "disease gene-drug target" network analysis, which were verified by a series of in vivo experiments. JTF administration effectively reduced pain and joint edema, inhibited matrix degradation, chondrocyte apoptosis, and aquaporin expression in OA rats. Notably, JTF dose-dependently reversed damage-associated molecular patterns and inflammatory factor upregulation. Mechanically, our "disease gene-drug target" network analysis indicated that the NCOA4-HMGB1-GSK3B-AQPs axis, implicated in ferroptosis and aquaporin dysregulation, may be potentially served as a target of JTF against OA. Accordingly, JTF mitigated NCOA4, HMGB1, and GSK3B expression, oxidative stress, and iron metabolism aberrations in OA rats. Furthermore, JTF treatment significantly attenuated the aberrant upregulation of AQP1, AQP3, and AQP4 proteins observed in cartilage tissues of OA rats. Our data reveal for the first time that JTF may exert cartilage protective and anti-edema effects in osteoarthritis therapy by inhibiting NCOA4-HMGB1-driven ferroptosis and aquaporin dysregulation.
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