Autophagy plays a protective role in advanced glycation end products-induced apoptosis of chondrocytes via regulation of tumor necrosis factor-α,nuclear factor-κ B and reactive oxygen species

摘要

Objective: To study the adverse effects of advanced glycation end products (AGEs) on chondrocytes and the role of autophagy in this process. Methods: Chondrocytes were harvested from the human articular cartilage tissues in surgery. AGEs were administered during chondrocytes culture. The rapamycin was used to induce autophagy. The cell viability was determined by 3-[4,5-dimethylthiazol2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. The expression of tumor necrosis factor-a (TNF-α) and nuclear factor-κB (NF-κB) was detected by quantitative real-time polymerase chain reaction. The reactive oxygen species (ROS) production and apoptosis of the chondrocytes were determined by fluorescent probe and flow cytometer,respectively. Results: The chondrocytes viability was significantly reduced after 12 h incubation with AGEs (P＜0.0l). In contrast, rapamycin pretreatment increased the chondrocytes viability through autophagy. AGEs increased TNF-α and NF-κB mRNA expression of chondrocytes and autophagy receded or proceeded the change. AGEs increased intracellular ROS accumulation and autophagy reversed the change. AGEs accelerated chondrocytes apoptosis and autophagy suspended apoptosis. Conclusions: Accumulation of AGEs may have an adverse role for chondrocytes by increasing TNF-α and NF-κB expression, ROS accumulation and apoptosis; meanwhile, autophagy ameliorates the AGEs-induced adverse effects.