Though changes in normal joint motions and loads (e.g., following anterior cruciate ligament injury) contribute to the development of knee osteoarthritis, the precise mechanism by which these changes induce osteoarthritis remains unknown. The goal of the study is to turn the articular cartilage in a healthy knee model into the articular cartilage of an osteoarthritic ACL-injury knee by imposing the ACL-injury kinematics on the healthy knee model. To achieve that goal, this study was performed in 2 main steps:​ a) we evaluated different computational methods for simulating in vitro articular cartilage wear in the PF joint, b) we evaluated the cartilage adaptation law in the idealized joint model as well as the patient-specific tibiofemoral joint model. The first evaluation used a unique combination of experimental, computational, and imaging techniques to provide the first published comparison between experimentally measured and computationally simulated cartilage wear patterns for the same knee and laid a solid technical foundation for the second evaluation. The second evaluation proposed a novel empirical cartilage adaptation law that can qualitatively predict the primary OA characteristics in a patient-specific model with the help of MRI and fluoroscopy. To echo the need of a mechanism of cartilage OA development due to ACL-injury, this study proposed a theory as well as knead a framework that can predict both in vitro and in vivo cartilage adaptation. The systematic methodology, once refined, can be extended to identify knee OA risk, to prevent OA initiation and even to slow down OA progression.