Avicularin suppresses cartilage extracellular matrix degradation and inflammation via TRAF6/MAPK activation

• Published in: Phytomedicine (Stuttgart) 2021-10, Vol.91, p.153657-153657, Article 153657
• Main Authors: Zou, Zi-ling, Sun, Ming-hui, Yin, Wei-feng, Yang, Lei, Kong, Ling-yi
• Format: Article
• Language: English
• Subjects: Avicularin; Extracellular matrix degradation; inflammation; Osteoarthritis; TRAF6
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2021.153657

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. [Display omitted]