Kruegel J et al. –Both nidogen-1 and nidogen-2 proteins play a key role in the pathogenesis of OA and either could be applied as a diagnostic marker. Methods
Aim was to investigate the presence and function of nidogen-1 and nidogen-2 in healthy human cartilage and in late-stage osteoarthritis (OA) cartilage
The location and quantity of nidogen-1 and nidogen-2 protein and mRNA were determined in cartilage tissue IHC, in situ hybridization, and RT-PCR
Adhesion and inhibition assays, a pre-embedding method, fluorescence-activated cell sorting, and ultrastructural investigations with integrins were also carried out
Results
Developing tissue from human embryos showed strong staining for both nidogens in condensed mesenchyme and in rib anlagen
Homogeneous staining for nidogen-1 was observed in the extracellular matrix of healthy articular cartilage, whereas nidogen-2 was localized pericellularly
In late-stage OA cartilage, expression of nidogen-1 was decreased pericellularly around diseased chondrocytes, whereas nidogen-2 was increased
However, both nidogens had strongly increased levels around elongated chondrocytes, especially in areas of deep surface fissures
In vitro, both nidogens functioned as adhesion proteins for cells from the OA defect
In vivo, colocalizations with integrins α v and β1 as well as internalization of nidogens by chondrocytes in vitro were observed
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