期刊
OSTEOARTHRITIS AND CARTILAGE
卷 16, 期 7, 页码 756-763出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.joca.2007.10.009
关键词
cartilage; antioxidant enzyme; oxidative stress; chondrocytes; osteoarthritis
Objective: Beside matrix metalloproteinases, reactive oxygen species (ROS) are the main biochemical factors of cartilage degradation. To prevent ROS toxicity, chondrocytes possess a well-coordinated enzymatic antioxidant system formed principally by superoxide dismutases (SODs), catalase (CAT) and glutathione peroxidase (GPX). This work was designed to assess the effects of interleukin (IL)-1 beta and IL-6 on the enzymatic activity and gene expression of SODs, CAT and GPX in bovine chondrocytes. Methods: Bovine chondrocytes were cultured in monolayer for 4-96 h in the absence or in the presence of IL-1 beta (0.018-1.8 ng/ml) or IL-6 (10-100 ng/ml). To study signal transduction pathway, inhibitors of mitogen-activated protein kinases (MAPK) (PD98059, SB203580 and SP600125) (5-20 mu M) and nuclear factor (NF)-kappa B inhibitors [BAY11-7082 (1-10 mu M) and MG132 (0.1-10 mu M)] were used. SODs, CAT and GPX enzymatic activities were evaluated in cellular extract by using colorimetric enzymatic assays. Mn SODs, Cu/Zn SOD, extracellular SOD (EC SOD), CAT and GPX gene expressions were quantified by real-time and quantitative polymerase chain reaction (PCR). Results: Mn SOD and GPX activities were dose and time-dependently increased by IL-1 beta. In parallel, IL-1 beta markedly enhanced Mn SOD and GPX gene expressions, but decreased Cu/Zn SOD, EC SOD and CAT gene expressions. Induction of SOD enzymatic activity and Mn SOD mRNA expression were inhibited by NF-kappa B inhibitors but not by MAPK inhibitors. IL-6 effects were similar but weaker than those of IL-1 beta. Conclusions: In conclusion, IL-1 beta, and to a lesser extend IL-6, dysregulates enzymatic antioxidant defenses in chondrocyte. These changes could lead to a transient accumulation of H2O2 in mitochondria, and consequently to mitochondria damage. These changes contribute to explain the mitochondrial dysfunction observed in osteoarthritis chondrocytes. (C) 2007 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据