Fig. 2. Theoretical model for the relationships of aging, oxidative stress, and the development of osteoarthritis.
Aging-related oxidative stress as well as abnormal biomechanical stress results in increased levels of reactive oxygen species (ROS) in chondrocytes. The increase in ROS modulates anabolic and catabolic signaling pathways resulting in reduced matrix synthesis, inhibition of growth factor expression, and increased production of matrix metalloproteinases (MMPs) and cytokines that lead to matrix loss and osteoarthritis. Aging also results in increased formation of advanced glycation end-products (AGEs) which causes increased fatigue failure of the cartilage that when stressed also contributes to the development of osteoarthritis.