LAUSR

Osteoarthritis (OA) is a common degenerative joint disease. The pathological changes of chondrocytes involve oxidative stress, the pro‐inflammatory response, and pro‐apoptotic events. Galectin‐3 (Gal‐3) is a 35 kDa protein with a special chimeric structure. Gal‐3 participates in the progression of many diseases, such as cancer metastasis and heart failure. A previous study demonstrated that Gal‐3 expression in human cartilage with OA is increased. However, the role of Gal‐3 in chondrocyte dysfunction in joints is still unclear. In this study, we applied Gal‐3 (5–20 μg/ml) to TC28a2 human chondrocyte cells for 24 h to induce chondrocyte dysfunction. We found that Gal‐3 upregulated TLR‐4 and MyD88 expression and NADPH oxidase, thereby increasing intracellular ROS in the chondrocytes. Gal‐3 increased phosphorylated MEK1/2 and ERK levels, and promoted NF‐κB activity. This activation of NF‐κB was reduced by silencing TLR‐4 and NOX‐2. In addition, Gal‐3 caused apoptosis of chondrocytes through the mitochondrial‐dependent pathway via the TLR‐4/NADPH oxidase/MAPK axis. Our study proves the pathogenic role of Gal‐3 in Gal‐3‐induced chondrocyte dysfunction and injuries.