Lipopolysaccharide Induces Mitochondrial Oxidative Stress and Accelerates Apoptosis by Activating ROS/NF-κB in Osteoarthritis Chondrocytes

Abstract Background. Chondrocyte apoptosis plays a significant role in the pathogenesis of osteoarthritis (OA), but the mechanism remains unclear. This research aimed to elucidate the effect of mitochondrial oxidative stress on chondrocyte apoptosis through ROS/NF-κB pathway. Methods. Mouse chondrocytes exposed to lipopolysaccharide (LPS) were used as OA models in vitro. Cell viability was tested by CCK-8. Cell proliferation, apoptosis, reactive oxygen species (ROS), and mitochondrial membrane potential were detected by fluorescence microscopy or flow cytometry. Contents of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and adenosine triphosphate (ATP) were evaluated by biochemical detection. Ultrastructure of mitochondria was observed by transmission electron microscope (TEM). Relative mRNA and protein expression were detected by quantitative polymerase chain reaction (qPCR) and western blot. Results. LPS increased the level of ROS and activated the NF-κB pathway, which decreased cell viability, inhibited the activity of SOD/CAT/GSH, and induced mitochondrial oxidative stress. The disturbance of mitochondrial homeostasis decreased mitochondrial membrane potential and adenosine triphosphate (ATP), which eventually accelerated apoptosis. The ultrastructure of mitochondria changed with swelling, intrinsic vacuole, and deformed cristae after treated by LPS. These LPS-induced effects were attenuated by Pyrrolidinedithiocarbamate ammonium (PDTC, an NF-κB inhibitor) and N-acetylcysteine (NAC, an antioxidant). Conclusions. LPS can induce mitochondrial oxidative stress and accelerate apoptosis through the ROS/NF-κB pathway. As mitochondrial dysfunction is an early sign of apoptosis, regulating the redox state of chondrocytes and maintaining mitochondrial homeostasis may provide novel ideas for the early treatment of OA.