PI3K/Akt and caspase pathways mediate oxidative stress-induced chondrocyte apoptosis.

Chondrocyte apoptosis is closely related to the development and progression of osteoarthritis (OA); however, the underlying mechanisms remain enigmatic. Previous studies have confirmed that cell apoptosis is one of the main pathological alterations during oxidative stress, and chondrocyte apoptosis induced by oxidative stress plays an important role in the development of OA. Rat chondrocytes exposed to hydrogen peroxide (H2O2) were used as the experimental oxidative stress model. We assessed cell viability, cell apoptosis, levels of intracellular reactive oxygen species (ROS), nitric oxide (NO) production, gene relative expression level of inducible nitric oxide synthase (iNOS), and expressions of iNOS, PI3K, phospho-Akt, caspase-9, and caspase-3. With the rising of intracellular ROS and increasing iNOS synthesis, producing a large amount of NO in chondrocytes, H2O2 decreased the cell viability and induced cell apoptosis of chondrocytes. Furthermore, the levels of caspase-9 and caspase-3 protein expression were significantly elevated as well as the level of p-Akt protein expression when induced by oxidative stress. These findings suggest that oxidative stress-induced chondrocyte apoptosis occurred via activating both PI3K/Akt and caspase pathways in the early stage in these processes.