Structural and Compositional Changes in Peri- and Extracellular Matrix of Osteoarthritic Cartilage Modulate Chondrocyte Morphology

Abstract

It has not been shown how specific changes in composition and structure in the peri- and extracellular matrix (PCM and ECM) of human articular cartilage modulate cell morphology in different stages of osteoarthritis (OA). In the present study, cell morphology in the superficial tissue of normal, early OA and advanced OA human cartilage samples were measured from histological sections. Collagen and proteoglycan contents in the vicinity of chondrocytes were analyzed using Fourier transform infrared spectroscopy and digital densitometry. Determinants of the experimentally observed morphological changes of cells were studied using finite element analysis (FEA). From normal tissue to early OA, cell aspect ratio (height/width) remained constant (0.69 ± 0.11 and 0.69 ± 0.09, respectively). In advanced OA, cells became significantly (p < 0.05) more rounded (aspect ratio of 0.83 ± 0.13). Normalized collagen content in the PCM, i.e. collagen content in the PCM with respect to that in the ECM, was reduced significantly (p < 0.05) only in advanced OA. FEA indicated that reduced proteoglycan content and increased collagen fibrillation in the PCM and ECM, as well as reduced collagen content only in the PCM, primarily explained experimentally found changes in cell aspect ratio. Our results suggest that changes in composition and structure of the PCM and ECM in the superficial tissue of human articular cartilage modulate cell morphology differently in early and advanced OA.