Background – the joint disease osteoarthritis causes pain and disability in adults, and is one of our most common diseases. Osteoarthritis mainly affects the knee, hip and finger joints. There is no cure for osteoarthritis and the healthcare today is focused on pain management, physiotherapy, and in the end-stage joint replacement (prosthesis). Knee injuries (e.g. meniscus and cruciate ligament) are one of the few known risk factors for the development of knee osteoarthritis but the mechanisms behind the progress from injury to osteoarthritis is largely unknown.

The articular cartilage of the joints acts as friction and shock absorbers. The synovial fluid, found between the joint surfaces, is the lubricant in the joint and provides the cartilage with nutrients. The structural proteins (“building blocks”) of cartilage - aggrecan and collagen - together with the synovial fluid give the tissue its elastic shock-absorbing function. In a healthy cartilage there is a balance between formation and resorption of the different component of the tissue. During the development of osteoarthritis occurs an imbalance, and large quantities of enzymes are formed that degrade cartilage proteins. Aggrecan is one of the first cartilage proteins that are broken down in osteoarthritis, which is thereby released into the synovial fluid. High concentration of aggrecan and other cartilage proteins (e.g. COMP, collagen, SLRPs) in the synovial fluid may indicate of a molecular imbalance in the cartilage and therefore can be used as a molecular marker for osteoarthritis. Knowledge of the biological processes of joint injuries and the development of osteoarthritis is incomplete and more research is needed for a better understanding of these mechanisms.

Objective - By means of biochemical analysis and magnetic resonance imaging (MRI) follow the molecular and structural changes occurring at knee injuries and in osteoarthritis. We want to study the biological course of events in the joint at knee injuries that develop into osteoarthritis, and at different stages of the disease, analyze the relationships between molecular markers, MRI findings (examining the tissue structure) and symptoms (e.g. pain, joint stiffness).

Study design - From tissue-models of joint injuries for growing cartilage, and samples of blood, urine and synovial fluid from cross-sectional and longitudinal cohorts of patients (i.e. joint injury, osteoarthritis, rheumatoid arthritis and knee-healthy), we analyze (using immunological methods and mass spectrometry) the brake down products of bone and cartilage. We use MRI analysis of knee joints for structural and volume measurements of cartilage and other joint tissues, and patient evaluation questionnaires to gather information about symptoms like pain, joint-stiffness and quality of life (clinical data). Molecular markers are finally compared with the MRI analysis and clinical data.

Importance - The development of osteoarthritis is slow and we know too little about the early course of the disease. Clinical examination and X-rays are not sensitive enough tools for early detection of osteoarthritis. Molecular markers could be used for this purpose, but also to follow the course of disease and effect of treatment. In order to eventually be able to treat the disease osteoarthritis and its symptoms by example medicine with anti-retroviral effect for cartilage degradation, we must understand what enzymes and signal molecules that interact at the tissue breakdown and which molecules can promote the rebuilding of cartilage. By combining the results of analyzes of molecular-, structural- and patient-levels, we can identify the disease mechanisms and risk factors for osteoarthritis.

The project is carried out in collaboration between researchers in orthopedics, radiology, physiotherapy, cell biological and biochemical expertise. This composition gives us a unique opportunity to identify the disease process behind osteoarthritis.