Changes in stiffness of the extracellular and pericellular matrix of chondrocytes in human articular cartilage in the course of osteoarthritis

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Dokumentart: PhDThesis
Date: 2023-07-24
Language: English
Faculty: 4 Medizinische Fakultät
Department: Medizin
Advisor: Hofmann, Ulf Krister (Prof. Dr.)
Day of Oral Examination: 2023-04-11
DDC Classifikation: 000 - Computer science, information and general works
420 - English and Old English
610 - Medicine and health
Keywords: Arthrose , Hyaliner Knorpel , Knorpelzelle
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OA is one of the most common joint pathologies worldwide, characterized by progressive cartilage degeneration, causing chronic pain and physical disability. The OA-related collagen destruction of the cartilage alters its biomechanical properties and consequently limits the cartilage function in load transmission and shock absorption, which is necessary for its physiological functioning. The detailed pathophysiology of OA is only partly understood, which is one reason for the lack of targeted therapy options. The present study aimed to investigate biomechanical and structural osteoarthritic changes of human articular cartilage of the knee joint and their relation to changes in spatial chondrocyte organization, which have been suggested as an image-based biomarker for the severity of OA degeneration. The present study investigated articular cartilage samples of 30 patients diagnosed with advanced knee OA who underwent total knee arthroplasty. Cartilage samples of the femoral condyles were assessed through AFM. Stiffness measurements took place in ECM and PCM regions of the different spatial chondrocyte patterns (SS, DS, SC, BC). Immunofluorescence analysis of collagen type I and II was conducted to evaluate structural changes of both matrices qualitatively. AFM stiffness measurements showed that changes in the spatial chondrocyte organization strongly correlate with the stiffness of the ECM and PCM. A significant reduction in the stiffness for both matrices with each change of cellular pattern was observed, except for the change from single to double string for the ECM (p = 0.072). In the immunofluorescence analysis, collagen type II remodeling into collagen type I could gradually be observed in the course of OA when using spatial chondrocyte organization as an OA biomarker. The present study is the first to describe stiffness changes of the ECM in relation to the PCM and changes in spatial chondrocyte organization quantitatively. The findings imply that OA affects the ECM and PCM simultaneously and to a comparable extent, suggesting that their degeneration process underlies the same destructive pathophysiological mechanism.

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