Advanced oxidation protein products induce apoptosis of human chondrocyte through reactive oxygen species‐mediated mitochondrial dysfunction and endoplasmic reticulum stress pathways

作者：Wenbin Ye, Siyuan Zhu, Congrui Liao, Jun Xiao, Qian Wu, Zhen Lin, Jian-Ting Chen · 发表于：Fundamental and Clinical Pharmacology · 年份：2016 · DOI：10.1111/fcp.12229 · 被引用次数：48 · 研究领域：Endoplasmic Reticulum Stress and Disease、Rheumatoid Arthritis Research and Therapies、Adenosine and Purinergic Signaling

Advanced oxidation production products (AOPPs) have been confirmed to accumulate in patients with rheumatoid arthritis (RA). Previous study demonstrated that AOPPs could accelerate cartilage destruction in rabbit arthritis model. However, the effect of AOPP stimulation on apoptosis of human chondrocyte and the underlying mechanisms remains unclear. This study demonstrated that exposure of chondrocyte to AOPPs resulted in cell apoptosis. AOPP stimulation triggered reactive oxygen species (ROS) production, which induced mitochondrial dysfunction and endoplasmic reticulum stress (ER stress) resulted in caspase activation. Furthermore, an antioxidant, N-acetylcysteine, markedly blocked these signals. Our study demonstrated that AOPPs induce apoptosis via ROS-related mitochondria- and ER-dependent signals in human chondrocyte. Targeting AOPP-triggered ROS generation might be as a promising option for patients with RA.