title: Effect of Laminin-A4 inhibition on cluster formation of human osteoarthritic chondrocytes.
abstract: Formation of chondrocyte clusters is not only a morphological sign of osteoarthritis but it is also observed in cell culture. Active locomotion of chondrocytes is controlled by integrins in vitro. Integrins bind to Laminin-A4 (LAMA4), a protein that is highly expressed in vivo in clusters of hypertrophic chondrocytes. We tested if LAMA4 is relevant for cluster formation. Human chondrocytes were cultured in a 2D matrigel model and treated with different concentrations of a monoclonal inhibitory anti-LAMA4-antibody. Migration and cluster formation was analysed using live cell imaging technique. Full genome gene expression analysis was performed to assess the effect of LAMA4 inhibition. The data set were screened for genes relevant to cell motility. F-actin staining was performed to document cytoskeletal changes. Anti-LAMA4 treatment significantly reduced the rate of cluster formation in human chondrocytes. Cells changed their surface morphology and exhibited fewer protrusions. Expression of genes associated with cellular motility and migration was affected by anti-LAMA4 treatment. LAMA4-integrin signalling affects chondrocyte morphology and gene expression in vitro, thereby contributing to cluster formation in human osteoarthritic chondrocytes.
authors: Division of Rheumatology and Immunology, Medical University Graz.
authors: Florentine C
authors: FC
authors: Moazedi-Fuerst
authors: Department of Orthopaedic Surgery, Medical University Graz.
authors: Gerald
authors: G
authors: Gruber
authors: Division of Rheumatology and Immunology, Medical University Graz.
authors: Martin H
authors: MH
authors: Stradner
authors: Department of Molecular Medicine, Section of Anatomy, University of Padua.
authors: Diego
authors: D
authors: Guidolin
authors: Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago.
authors: Jonathan C
authors: JC
authors: Jones
authors: Department of Pathology, Medical University Graz.
authors: Koppany
authors: K
authors: Bodo
authors: Center of Medical Research, Corefacility Molecular biology, Medical University Graz.
authors: Karin
authors: K
authors: Wagner
authors: Division of Rheumatology and Immunology, Medical University Graz.
authors: Daniela
authors: D
authors: Peischler
authors: Division of Rheumatology and Immunology, Medical University Graz.
authors: Verena
authors: V
authors: Krischan
authors: Division of Rheumatology and Immunology, Medical University Graz.
authors: Jennifer
authors: J
authors: Weber
authors: Department of Orthopaedic Surgery, Medical University Graz.
authors: Patrick
authors: P
authors: Sadoghi
authors: Department of Orthopaedic Surgery, Medical University Graz.
authors: Mathias
authors: M
authors: Glehr
authors: Department of Orthopaedic Surgery, Medical University Graz.
authors: Andreas
authors: A
authors: Leithner
authors: Division of Rheumatology and Immunology, Medical University Graz.
authors: Winfried B
authors: WB
authors: Graninger
mesh_terms: D000368:Aged; D002465:Cell Movement; D002478:Cells, Cultured; D019902:Chondrocytes / Q000502:physiology*; D005260:Female; D006801:Humans; D016023:Integrins / Q000378:metabolism; D007797:Laminin / Q000378:metabolism*; D008875:Middle Aged; D010003:Osteoarthritis / Q000503:physiopathology*
chemical_list: D016023:Integrins; C501369:LAMA4 protein, human; D007797:Laminin
keywords: LAMA4; chondrocytes; cluster; migration; osteoarthritis