Benzophenone-3 exposure induced apoptosis via impairing mitochondrial function in human chondrocytes

Osteoarthritis (OA) is a chronic joint disease affecting millions of adults worldwide, characterized by degeneration of articular cartilage. Many environmental risk factors contribute to OA development. Benzophenone-3 (BP-3), a commonly used ultraviolet filter in personal care products, has been positively associated with OA risk. However, it remains unclear whether and how BP-3 induces toxic effects on articular chondrocytes and promote OA development. This study aims to investigate the damage of BP-3 at environmentally relevant concentrations to human chondrocytes, as well as potential mechanisms linking BP-3 with injury of chondrocytes. Notably, BP-3 significantly inhibited cell viability, induced apoptosis, and up-regulated matrix metalloproteinase (MMP) 1 and 13 which mediated cartilage degradation in C28/I2 human normal chondrocytes. Moreover, the function of mitochondria was impaired and oxidative stress occurred in BP-3 exposure groups, evidenced by elevation of reactive oxygen species (ROS) generation, reduction of mitochondrial membrane potential, decrease of ATP production and inhibition of mitochondrial respiratory chain complex I, II, III and IV. Meanwhile, BP-3 caused mitochondrial cristae vague and formation of autophagosomes. PTEN induced putative kinase 1/E3 ubiquitin protein ligase (PINK1/Parkin) pathway was also activated by BP-3. Addition of autophagy inhibitor, 3-Methyladenine (3-MA), suppressed PINK1/Parkin-mediated mitophagy, but increased BP-3-induced expression of MMP1 and 13, as well as exacerbated BP-3-induced apoptosis, suggesting mitophagy may exert a chondroprotective effect and partially alleviate apoptosis induced by this compound. In brief, BP-3 exposure may increase OA risk via inducing apoptosis and increasing breakdown of extracellular matrix in chondrocytes, and mitochondrial dysfunction and mitophagy may play a crucial role in the mechanisms of BP-3-induced toxicity to articular chondrocytes.