Zafirlukast, a leukotriene receptor antagonist, has been shown to exert a wide range of effects including anti-asthmatic, anti-inflammatory and oral anti-bacterial. Osteoarthritis is one of the most prevalent age-related public health burdens in the modern world. In the present study, we applied zafirlukast in the treatment of human primary chondrocytes and found that it exerts potent anti-osteoarthritic effects. Zafirlukast inhibited AGEs-induced degradation of the articular extracellular matrix by suppressing expression of MMPs, ADAMTS, NOX-4, generation of ROS, and activation of NF-κB via the IκBα/JNK/AP-1 pathway through targeted inhibition of CysLTR1. These findings suggest that zafirlukast possesses a protective effect against AGEs- induced damage and dysfunction in human chondrocytes.
Keywords: AGEs; Articular ECM; NF-κB; NOX-4; Osteoarthritis; Zafirlukast.
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