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

Abstract

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- α (TNF- a ) and nuclear factor- κ B (NF- κ B) 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<0.01)). In contrast, rapamycin pretreatment increased the chondrocytes viability through autophagy. AGEs increased TNF- α and NF- κ B 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- κ B expression, ROS accumulation and apoptosis; meanwhile, autophagy ameliorates the AGEs- induced adverse effects.

Keywords

• advanced glycation end products
• autophagy
• tumor necrosis factor- α
• nuclear factor- κ b
• reactive oxygen species
• apoptosis
• chondrocytes