OA is the most common form of arthritis worldwide. Chronic low-grade inflammation in the articular environment causes cartilage degeneration at an early disease stage, resulting in chronic pain, disability and loss of independence due to progressive joint destruction. To date, no disease modifying treatment is available to sustainably combat low-grade inflammation in early-stage OA patients. Biomechanical causes for intra-articular inflammation and OA development have been detected in specific patient groups. The PROTO consortium strives to implement new evidence- and patient-centered treatment strategies for early- and pre-disease stages. For the first time, early-stage knee OA patients will be treated with local PLX-PAD injections, a novel allogeneic cell therapy product with distinct anti- inflammatory capacities that may halt or revert disease progression. Secondly, patients recovering from anterior cruciate ligament reconstructions with pathological gait patterns leading to knee OA, will be treated with a personalized sensor-based digital training intervention.