Extrazelluläre Matrixproteine des humanen Gelenkknorpels und deren Bedeutung als Biomarker vermehrter mechanischer Gelenkbelastung

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Osteoarthritis (OA) is one of the most important musculoskeletal disorders. However, the pathogenesis of OA is still not completely understood. Changes in the local biomechanical loading environment of the joint have been shown to increase the risk of gonarthrosis. Unfortunately, we are unable to distinguish between functional and pathomechanical joint loading patterns.
OA biomarkers are matrix components and/or their breakdown products, cytokines and proteases that can be analyzed in synovial fluid, blood serum or urine. They might have the potential to detect critical events in cartilage metabolism and thereby identify pathomechanical joint loading. Perifibrillar adapter proteins gained in importance as potential OA biomarkers. They are essential for healthy articular cartilage, as they play a crucial role in proper collagen fibril formation, collagen network stabilization, and the interconnection between the fibrillar and extrafibrillar matrix. One of the most studied OA biomarkers is cartilage oligomeric matrix protein (COMP). Increased COMP levels could be observed in blood serum of patients suffering from OA, and it has been shown that an increase in the serum COMP level reflects progressive joint damage, OA severity and numbers of joints affected. Furthermore, serum COMP is increased in healthy humans after physical activity. However, the exact mechanisms are still unknown.
Therefore, the aim of our first study was to analyze the extracellular distribution of four major perifibrillar adapter proteins, namely collagen IX, decorin, matrilin-3, and COMP, including that of collagen II (as the primary component of the fibrillar matrix) in healthy and osteoarthritic human knee joint cartilage, and to relate the distribution patterns in OA cartilage to the disease stage. In two subsequent studies we aimed to examine the effect of an increase in mechanical knee joint loading during 30 minutes of running on the serum COMP level and the fragmentation pattern, and identify correlations between mechanical parameters of knee joint loading and the change in serum COMP level.
Perifibrillar adapter proteins might play a greater role in the pathogenesis of OA than previously thought. Our immunohistological analyses indicate that, in the course of OA, the mechanical stabilization of the extracellular matrix (ECM) through crosslinking of the collagen network in the upper zones of cartilage is being destroyed, due to a loss of perifibrillar adapter proteins. Unfortunately, the underlying mechanisms remain still unclear. However, mechanical loading of cartilage seems to play an important role. Immediately after running with and without additional knee joint load, a significant increase in serum COMP levels could be observed. In this context there was evidence of a greater impact of a change in joint kinematics on serum COMP level than of an increase in knee joint moments. In addition, our fragment analyses have shown that both running interventions lead to an increase in COMP fragments in serum. In turn, this might give an indication for a mechanical breaking out of COMP from the ECM of articular cartilage, due to an increased mechanical joint loading while running. The time of COMP release into circulation and its degradation seem to be differently regulated by various knee joint loading characteristics. Breaking out of perifibrillar adapter proteins from the ECM might be one of the first responses of cartilage on mechanical joint loading. In order to use serum COMP as a biomarker of cartilage degradation in future, studies determining the critical limit of COMP degradation leading to an irreparable damage of the ECM are required.
Original languageGerman
Place of PublicationKöln
PublisherDeutsche Sporthochschule Köln
Number of pages35
Publication statusPublished - 2019