The results indicate a relation between structural, mechanical and histological changes in all stages of the degeneration. With increasing ICRS Grade the cartilage stiffness, which is primarily influenced by the integrity of the extracellular matrix, decreases. Therefore, methods of stiffness determination such as indentation may be used to characterize cartilage in all stages of OA. However, the data suggest that differentiating between healthy cartilage and ICRS Grade 1 may be difficult using mechanical testing alone.