Traumatic injuries in human joints can cause cartilage degeneration and lead to post-traumatic osteoarthritis. Few techniques are now available in practice to prevent the cartilage from degeneration after the joint injuries. Our research discovered that statins, a class of drugs used by 40 million US people to control the cholesterol levels, can effectively protect the cartilage from various OA-inducing factors. We found that statins can directly act on the cartilage cells and prevent them from degrading the cartilage matrix. In this project, we will determine the efficacy and mechanism of statins for the prevention of post-traumatic osteoarthritis. First, using a retrospective cohort study, we will determine the correlation between statin use and OA occurrence among the Delaware population. Second, using in vitro cell/tissue culture models, we will identify the cartilage- protective mechanisms of statin. Third, we will test the efficacy of statin for PTOA prevention using animal models. Outcome of this project can provide us justifications for the clinical trials of statin application on the patients with joint injuries. The long-term goal of this project is to pursuit an FDA approval for the repurpose of statins in joint treatment and PTOA prevention. If this project is successful, it will immediately increase the prescription adherence of 40 million current statin users, especially those at a high risk of osteoarthritis occurrence with a joint injury history. Few therapeutic techniques are available for the prevention of osteoarthritis after the traumatic joint injuries. This project will determine the efficacy of statins, a class of drugs for cholesterol control, for the prevention of osteoarthritis. Outcome of this project could be one of the first effective pharmaceutical solutions for osteoarthritis prevention.