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Regular physical activity has been suggested as having both preventive and therapeutic benefits for individuals with osteoarthritis (OA). However, evidence of whether exercise and which type of exercise constitutes a benefit or a risk in the development and progression of OA remains debatable. Cartilage expresses cell surface markers that can provide information as to in what way OA develops. The purpose of this presentation is to provide further insight based on OA biomarkers and the role physical activity plays in the management of OA. Osteoarthritis biomarkers together with radiographic imaging evidence will ideally guide healthcare providers to incorporate exercise recommendations into clinical management and offer patients evidence-based and individually tailored exercise prescriptions.