Activation of autophagy contributes to the protective effects of lycopene against oxidative stress-induced apoptosis in rat chondrocytes.

Abstract

Oxidative stress is commonly associated with osteoarthritis (OA). Lycopene (LYC), a natural carotenoid compound, is an effective antioxidant with potential cartilage-protecting actions. However, how it affects hydrogen peroxide (H2 O2 )-induced damage to the cartilage is unclear. In this study, an in vitro oxidative stress model was developed via treating primary chondrocytes with H2 O2 . Western blot, immunohistochemistry, and quantitative RT-PCR (qRT-PCR) were used to assess the levels of related factors. Reactive oxygen species (ROS) and apoptosis levels were analyzed by the use of appropriate probes and flow cytometry. The expression and activity of stress-specific enzymes (malondialdehyde, superoxide dismutase, and catalase) were also assessed. The role of autophagy was explored by using the inhibitor, 3-methyladenine (3-MA), as well as monodansylcadaverine staining, western blotting, and red fluorescent protein-green fluorescent protein-light chain 3 lentivirus infection. The result showed LYC exerted significant chondrocyte-protective effects, including reduced inflammation and chondrocyte degradation, increased chondrocyte proliferation, apoptosis inhibition, and reduced ROS production. LYC could effectively induce autophagy in the H2 O2 treatment group, and this effect could be attenuated by 3-MA. In terms of mechanism, LYC played a role in inhibiting MAPK and PI3K/Akt/NF-κB axis, which down-regulates levels of mTOR and had a potential therapeutic significance for cartilage degeneration.