化学
骨关节炎
MAPK/ERK通路
细胞生物学
炎症
细胞外基质
肿瘤坏死因子α
软骨
阿格里坎
信号转导
癌症研究
分子生物学
药理学
医学
病理
免疫学
生物化学
生物
解剖
关节软骨
替代医学
作者
Ziling Zou,Ming‐Hui Sun,Yin Wu,Lei Yang,Ling‐Yi Kong
出处
期刊:Phytomedicine
[Elsevier]
日期:2021-10-01
卷期号:91: 153657-153657
被引量:25
标识
DOI:10.1016/j.phymed.2021.153657
摘要
Osteoarthritis (OA) is an intractable degenerative disease of the whole joint, which is characterized by synovitis inflammation, cartilage damage, and chronic pain. Tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) performs an important role in OA. We aim to investigate avicularin to protect cartilage extracellular matrix degradation (ECM) and suppresses inflammation both in rat and human chondrocytes. 5-Ethynyl-2′-deoxyuridine (EdU) staining, Quantitative real-time PCR, TRAF6 plasmid transfection, Western blot, Measurement of nitric oxide (NO), ROS detection and Immunofluorescence were utilized in vitro. micro-CT scanning, Safranin O-Fast Green, toluidine blue and immunohistochemistry staining were performed in vivo. In vitro, avicularin attenuates the degradation of ECM and inflammation, which could inhibit the activation of TRAF6/MAPK pathway via targeting TRAF6. Increased MMP3 and MMP13 expressions and decreased Aggrecan and Collagen Ⅱ levels were observed in anterior cruciate ligament transection (ACLT) induced osteoarthritic rats. Interestingly, intra-articular injection of avicularin attenuates this phenomenon. Taken together, our results indicate that avicularin suppresses cartilage extracellular matrix degradation and inflammation via TRAF6/MAPK activation by targeting TRAF6. These observations identify TRAF6 as a relevant drug target, and avicularin may as a potential therapeutic agent in osteoarthritis.
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