Fig. 5

Schema of the cystine-cysteine cycle in knee osteoarthritis. Under excessive oxidative stress, cysteine is oxidized by hydrogen peroxide to cystine and transported into cells via the cystine-glutamate exchange transporter in the plasma membrane, and the transported cystine is intracellularly reduced to cysteine and used for the synthesis of proteins and glutathione. Glutathione has important roles in reducing reactive oxygen species. Increased extracellular cystine levels reflect the presence of oxidative stress in or around cells. Glutamate released via the cystine-glutamate transporter damages the chondrocytes, and high glutamate levels in the synovial fluid are accompanied by severe joint destruction in animal models of osteoarthritis. Although excessive oxidative stress can be controlled via the cystine-cysteine cycle, higher glutamate would also result in worse metabolic conditions for joint homeostasis