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OAPROGRESS Report Summary

Project ID: 281180
Funded under: FP7-IDEAS-ERC
Country: Finland

Final Report Summary - OAPROGRESS (Evaluation of Osteoarthritis Progression in a Patient-Specific Manner using Magnetic Resonance Imaging and Computational Modeling)

Osteoarthritis is one of the most prevalent disorders of the musculoskeletal system. In Europe, over 40 million people have osteoarthritis. In osteoarthritis, articular cartilage degenerates and eventually wears out, resulting in pain and disability. It is a major challenge in health care to prevent osteoarthritis or slow down the progression of the disease. The onset of osteoarthritis may result from an altered stress and strain state in cartilage, e.g., due to an injury of ligament, cartilage, or meniscus. However, the disease progression is patient-specific and can hardly be predicted. In order to assess the articular cartilage function and possible failure sites in joints, and to evaluate the onset and progression of osteoarthritis patient-specifically, computational models has become a potential quantitative option. In this project, we have developed and validated these models that may eventually become to clinical use.

Main findings of the project can be divided in to 5 parts/WPs:
WP 1: With the use of our developed computational model, we were able to analyze the mechanical characteristics of all major constituents of articular cartilage in the knee joint, those are collagen fibrils, proteoglycans and water. In particular, we were able to implement collagen fibril architecture and proteoglycan distribution of cartilage in the knee joint from MRI in a patient-specific manner. It was shown that these both patient-specific features modify local stress concentrations in the knee, which subsequently may lead to different diagnosis/estimation of possible failure sites in joints.

WP 2: Our simulation results suggest that anterior radial tear of meniscus causes the highest risk for the development of total meniscal rupture (compared to other tear types). The results also indicated that bilateral or partial meniscectomy might initiate a post-traumatic osteoarthritis rather from the lateral than medial compartment of the knee joint. Highest risks for meniscus and cartilage failures due to meniscus tear or meniscectomy, respectively, are suggested to occur during the loading response and mid-stance of the gait cycle (up to 50% of one walking cycle). Additionally, the computational models showed quantitatively that anterior cruciate ligament rupture causes particularly increased anterior translation of the femur, and that with a proper choice of the graft properties and pre-strain, there is a possibility to restore normal joint motion. This analysis could provide crucial information for an orthopaedist to prevent the onset and progression of osteoarthritis for this patient group.

WP 3: We showed that osteoarthritis progresses in the rabbit knee joint in a very site-specific manner, most changes in cartilage structure (especially those in collagen orientation and proteoglycan content) occurring in lateral femoral condyles. Consistently, our results obtained from human samples indicated that during osteoarthritis cell shape is primarily modulated by collagen fibril orientation. Surprisingly, we noticed that collagen content was increased in early stage of the disease in rabbits, suggesting up-regulation of cell synthesis. We also showed that cell deformation behavior (which contributes to cartilage health) is distinctly different for normal and osteoarthritic cartilage. Our cell level modeling was able to give explanations for this altered cell deformation behavior. Those were reduced proteoglycan content in the vicinity of cells and altered collagen fibril stiffness. It appears that if collagen could be regenerated quicker, or cells could accelerate the production of proteoglycans in early osteoarthritis (or if there was a therapeutic intervention that could concentrate on the cell environment), early changes in osteoarthritis could possibly be reversed.

WP 4, 5: By combining the develop methodology and results from earlier WPs, we were able to develop a method to predict changes in cartilage properties during OA progression. In particular, we were able to predict the progression of osteoarthritis for overweight subjects, while normal weight subjects did not develop osteoarthritis.

Ultimate achievement: We developed a method that was able to predict the progression of osteoarthritis in the knee (Mononen ME et al. Scientific Reports 6: 21415, 2016). This method could help in decision making of clinical treatments and interventions (conservative or surgical) for the prevention or further progression of OA.

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