The significance of the extracellular matrix proteins COMP and collagen IX in the mechanical function of articular cartilage and in the pathogenesis of osteoarthritis

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Osteoarthritis, the most common degenerative joint disease worldwide, is characterized by an imbalance between synthesis and degradation of the extracellular matrix (ECM) in articular cartilage. The ECM is composed of the proteoglycan aggrecan and heterotypic fibrils consisting of collagen II and XI. These two suprastructures are organized together with various non-collagenous glycoproteins in a molecular network that determines the mechanical properties of the tissue thereby defining its function. In recent years, we have worked intensively on two proteins interconnecting the two suprastructures, the glycoprotein cartilage oligomeric matrix protein (COMP) and collagen IX. Both proteins are localized at the surface of collagen fibrils and play a key role as adapter molecules mediating the integrity of the ECM. Further, their expression is mechanosensitive and they regulate the formation and diameter of collagen fibrils. This suggests that COMP and collagen IX are important for the mechanotransduction and integrity of articular cartilage. The aim of this project is to characterize their role in detail in mouse models and cell culture models. We hypothesize that both proteins contribute to the pathogenesis of osteoarthritis induced by mechanical stress. Both cellular and molecular biology techniques will be used. The long-term goal is to gain more insight into the biomechanical function of adapter molecules in cartilage function to better understand the development of osteoarthritis and to generate new treatments for this disease.