Methods are provided for evaluating osteoarthritis (OA), for example for diagnosing OA, to confirm a diagnosis of OA, to assess or prognose progression of OA, determining the severity of a subject who has OA, and determining a subject's risk of developing OA in the future, as are arrays and kits that can be used to practice the methods. In particular examples, the method includes determining an amount of activity (such as an amount of protein present or an amount of expression) of OA risk-related molecules, such as soluble vascular adhesion protein 1 (sVAP-1) or interleukin-15 (IL-15). Also provided are methods of identifying one or more compounds that alter the activity of an OA-related molecule, thereby identifying potential anti-osteoarthritis drugs.