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Expression of the VEGF receptor-3 in osteoarthritic chondrocytes: stimulation by interleukin-1β and association with β1-integrins

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Abstract

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 β1-integrin. Superficial osteoarthritic chondrocytes exhibited VEGFR-3 expression in the cytoplasm and on the cell membrane. Using western blotting we could demonstrate that interleukin-1β (IL-1β) 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 β1-integrin and VEGFR-3 in IL-1β-stimulated chondrocytes indicating that activated VEGFR-3 may interact with β1-integrin and associated subcellular pathways in osteoarthritic chondrocytes. Taken together with results of previous studies showing that β1-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 β1-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.

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Acknowledgements

The authors thank Mrs. S. Bramke for the execution of the immunohistochemical preparations. Mr. Jörg Romahn's and Mrs. Angelika Steuer's technical assistance is gratefully acknowledged. This work was supported by the Deutsche Forschungsgemeinschaft (For 308/2-1; DFG Grant Sh 48/2-4, Sh 48/2-5).

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Authors and Affiliations

  1. Institute of Anatomy, Medical Faculty Carl Gustav Carus, Technical University Dresden, Fiedlerstrasse 42, 01307, Dresden, Germany

    W. Schwab

  2. Institute of Anatomy, Freie Universität Berlin, Königin-Luise-Strasse 15, 14195, Berlin, Germany

    M. Shakibaei & G. Schulze-Tanzil

  3. Connective Tissue Research Group, Faculty of Veterinary Science, University of Liverpool, Liverpool, L69 7ZJ, UK

    A. Mobasheri

  4. Department of Orthopedic Surgery, Technical University Dresden, Fiedlerstrasse 42, 01307, Dresden, Germany

    T. Beichler

  5. Institute of Legal Medicine, Technical University Dresden, Fiedlerstrasse 42, 01307, Dresden, Germany

    J. Dressler

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  1. M. Shakibaei
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  2. G. Schulze-Tanzil
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  3. A. Mobasheri
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  4. T. Beichler
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  5. J. Dressler
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  6. W. Schwab
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Correspondence to W. Schwab.

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Shakibaei, M., Schulze-Tanzil, G., Mobasheri, A. et al. Expression of the VEGF receptor-3 in osteoarthritic chondrocytes: stimulation by interleukin-1β and association with β1-integrins. Histochem Cell Biol 120, 235–241 (2003). https://doi.org/10.1007/s00418-003-0558-8

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  • DOI: https://doi.org/10.1007/s00418-003-0558-8

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