Ye Wenbin, Zhong Zhaoming, Zhu Siyuan, Zheng Shuai, Xiao Jun, Song Shaolian, Yu Hui, Wu Qian, Lin Zhen, Chen Jianting
Department of Orthopaedic Spinal Surgery, Nanfang Hospital, Southern Medical University, China.
Department of Orthopedic Joint Surgery, Nanfang Hospital, Southern Medical University, China.
Int Immunopharmacol. 2016 Oct;39:149-157. doi: 10.1016/j.intimp.2016.07.018. Epub 2016 Jul 29.
Advanced oxidation protein products (AOPPs) have been shown to participate in the progression of rheumatoid arthritis (RA). However, the effect of AOPPs accumulation on catabolic effect in human chondrocyte and the underlying mechanism(s) remain unclear. The present study demonstrated that AOPPs inhibited cell viability and glycosaminoglycan (GAG) production in human chondrocyte. Exposure of chondrocyte to AOPPs significantly increased the production of catabolic factors, such as cyclooxygenase-2 (COX-2), matrix metalloproteinase 3 (MMPs)-3 and MMP-13. AOPPs stimulation induced ROS generation and NF-κ B p65 phosphorylation, which could be inhibited by soluble receptor for advanced glycan end products (sRAGE), NADPH oxidase inhibitor (apocynin), ROS scavenger (N-acetyl-cysteine, NAC). Furthermore, NF-κ B inhibitor Bay11-7082 significantly reversed the AOPPs-induced expression of catabolic factors and phosphorylation of NF-κ B p65. Targeting AOPPs-triggered catabolic effect might be as a promising option for patients with RA.
晚期氧化蛋白产物（AOPPs）已被证明参与类风湿性关节炎（RA）的病情发展。然而，AOPPs积累对人软骨细胞分解代谢作用的影响及其潜在机制仍不清楚。本研究表明，AOPPs抑制人软骨细胞的细胞活力和糖胺聚糖（GAG）生成。软骨细胞暴露于AOPPs会显著增加分解代谢因子的产生，如环氧合酶-2（COX-2）、基质金属蛋白酶3（MMPs）-3和MMP-13。AOPPs刺激诱导活性氧（ROS）生成和核因子κB p65磷酸化，而这可被晚期糖基化终末产物可溶性受体（sRAGE）、NADPH氧化酶抑制剂（夹竹桃麻素）、ROS清除剂（N-乙酰半胱氨酸，NAC）抑制。此外，核因子κB抑制剂Bay11-7082显著逆转AOPPs诱导的分解代谢因子表达和核因子κB p65磷酸化。针对AOPPs引发的分解代谢作用可能是RA患者的一个有前景的选择。
