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Expression of the VEGF receptor-3 in osteoarthritic chondrocytes: stimulation by interleukin-1 beta and association with beta 1-integrins.

Shakibaei, M, Schulze-Tanzil, G, Mobasheri, A, Beichler, T, Dressler, J and Schwab, W (2003) Expression of the VEGF receptor-3 in osteoarthritic chondrocytes: stimulation by interleukin-1 beta and association with beta 1-integrins. Histochem Cell Biol, 120 (3). pp. 235-241.

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Recent studies have demonstrated enhanced expression of vascular endothelial growth factor and vascular endothelial growth factor receptor (VEGFR)-1 and -2 in chondrocytes of rheumatoid and osteoarthritic cartilage. Since expression of VEGFR-3 ( Flt-4) in chondrocytes has not yet been investigated, we studied the distribution of VEGFR-3 in osteoarthritic cartilage samples by immunohistochemistry and immunoelectron microscopy. Furthermore, we looked for functional colocalization of VEGFR-3 with the signal transduction receptor beta(1)-integrin. Superficial osteoarthritic chondrocytes exhibited VEGFR-3 expression in the cytoplasm and on the cell membrane. Using western blotting we could demonstrate that interleukin-1 beta (IL-1 beta) stimulates the expression of VEGFR-3 in chondrocytes in vitro in a dose-dependent manner. By coimmunoprecipitation assay we found a functional complex between the beta(1)-integrin and VEGFR-3 in IL-1 beta-stimulated chondrocytes indicating that activated VEGFR-3 may interact with beta(1)-integrin and associated subcellular pathways in osteoarthritic chondrocytes. Taken together with results of previous studies showing that beta(1)-integrins were also associated with other surface receptors and proteins in chondrocytes that cause cartilage destruction in arthritis (for example, urokinase-type plasminogen activator receptor and matrix metalloproteinases), we can hypothesize that signal transduction by these receptor complexes via beta(1)-integrins may play a crucial role in pathogenesis of osteoarticular disorders. Further work needs to be done to elucidate downstream signaling events activated by these receptors.

Item Type: Article
Divisions : Surrey research (other units)
Authors :
Shakibaei, M
Schulze-Tanzil, G
Beichler, T
Dressler, J
Schwab, W
Date : September 2003
DOI : 10.1007/s00418-003-0558-8
Uncontrolled Keywords : Antigens, CD29, Cartilage, Articular, Cell Adhesion, Cell Membrane, Cells, Cultured, Chondrocytes, Cytoplasm, Humans, Interleukin-1, Microscopy, Immunoelectron, Osteoarthritis, Protein Binding, Signal Transduction, Vascular Endothelial Growth Factor Receptor-3
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 10:16
Last Modified : 24 Jan 2020 18:53

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