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

骨关节炎是世界范围内最常见的退行性关节疾病，其特征在于关节软骨细胞外基质（ECM）的合成和降解之间的失衡。ECM由蛋白聚糖聚集蛋白聚糖和由胶原II和Xi组成的异型原纤维组成。这两种超结构与各种非胶原糖蛋白一起组织在分子网络中，该分子网络决定组织的机械特性，从而定义其功能。近年来，我们集中研究了两种连接两种超结构的蛋白质，即糖蛋白软骨寡聚基质蛋白（COMP）和胶原IX。这两种蛋白质都位于胶原纤维的表面，并作为介导ECM完整性的衔接分子发挥关键作用。此外，它们的表达是机械敏感的，并且它们调节胶原原纤维的形成和直径。这表明COMP和胶原IX对于关节软骨的机械传导和完整性是重要的。该项目的目的是详细描述它们在小鼠模型和细胞培养模型中的作用。我们假设这两种蛋白质都参与了机械应力诱导的骨关节炎的发病机制。将使用细胞和分子生物学技术。长期目标是更深入地了解适配器分子在软骨功能中的生物力学功能，以更好地了解骨关节炎的发展，并为这种疾病提供新的治疗方法。

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.