BioProject

Background: Cluster formation of hypertrophic chondrocytes is a sign of late stage osteoarthritis. More...

Background: Cluster formation of hypertrophic chondrocytes is a sign of late stage osteoarthritis. In vitro chondrocytes have the ability to migrate on scaffolds. Important for motility issues in cartilage are integrines, part of the extracellular matrix, important for locomotory stimuli. The integrine Laminin4 is highly present in hypertrophic clusters of chondrocytes. We were interested if a blockade of LAMA4 is leading to less cluster formation. Methods: Human chondrocytes were cultured in a 2D matrixgel model and treated with different concentrations of a monoclonal anti-LAMA4-antibody.Migration habits were analysed using the cellobserver technique. An array analysis was performed before and after anti-LAMA4 treatment. The data set was screened for possible motility relevant genes. F-actin staining was performed to document cytoskeletal changes. Results: Anti-LAMA4 treatment reduced significantly the rate of cluster formation in human chondrocytes. Cells changed their surface promoting fewer extensions. Genes for motility and migration associated processes were differentially expressed by anti-LAMA4 treatment. Conclusion: LAMA4 blockade leads to less cluster formation in human chondrocytes in vitro. Anti-LAMA4 treatment suppresses filopodia expression, a possible explanation for less clustering. Interestingly anti-LAMA4 treatment seams to support a more milieu of earlier OA Overall design: human chondrocytes were analysed untreated, IL-1 treated and 2A3 antibody treated Less...