The Wnt antagonist Wif-1 interacts with CTGF and inhibits CTGF activity

Authors

  • Cordula Surmann-Schmitt,

    1. Department of Experimental Medicine I, Nikolaus-Fiebiger-Zentrum für Molekulare Medizin, University of Erlangen-Nuremberg, Germany
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  • Takako Sasaki,

    1. Department of Experimental Medicine I, Nikolaus-Fiebiger-Zentrum für Molekulare Medizin, University of Erlangen-Nuremberg, Germany
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  • Takako Hattori,

    1. Department of Biochemistry & Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmacy, 5-1 Shikata-cho, 2-chome, Okayama, Japan
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  • Nicole Eitzinger,

    1. Department of Experimental Medicine I, Nikolaus-Fiebiger-Zentrum für Molekulare Medizin, University of Erlangen-Nuremberg, Germany
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  • Georg Schett,

    1. Department of Internal Medicine 3, Erlangen Medical School, University of Erlangen-Nuremberg, Germany
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  • Klaus von der Mark,

    1. Department of Experimental Medicine I, Nikolaus-Fiebiger-Zentrum für Molekulare Medizin, University of Erlangen-Nuremberg, Germany
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  • Michael Stock

    Corresponding author
    1. Department of Experimental Medicine I, Nikolaus-Fiebiger-Zentrum für Molekulare Medizin, University of Erlangen-Nuremberg, Germany
    2. Department of Internal Medicine 3, Erlangen Medical School, University of Erlangen-Nuremberg, Germany
    • University of Erlangen-Nuremberg, Medical School, Nikolaus-Fiebiger-Zentrum für Molekulare Medizin, Department of Internal Medicine 3, Glückstr. 6, 91054 Erlangen, Germany.
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  • Cordula Surmann-Schmitt, Takako Sasaki and Takako Hattori contributed equally to this work.

Abstract

Wnt inhibitory factor 1 (Wif-1) is a secreted antagonist of Wnt signalling. We recently demonstrated that this molecule is expressed predominantly in superficial layers of epiphyseal cartilage but also in bone and tendon. Moreover, we showed that Wif-1 is capable of binding to several cartilage-related Wnt ligands and interferes with Wnt3a-dependent Wnt signalling in chondrogenic cells. Here we provide evidence that the biological function of Wif-1 may not be confined to the modulation of Wnt signalling but appears to include the regulation of other signalling pathways. Thus, we show that Wif-1 physically binds to connective tissue growth factor (CTGF/CCN2) in vitro, predominantly by interaction with the C-terminal cysteine knot domain of CTGF. In vivo such an interaction appears also likely since the expression patterns of these two secreted proteins overlap in peripheral zones of epiphyseal cartilage. In chondrocytes CTGF has been shown to induce the expression of cartilage matrix genes such as aggrecan (Acan) and collagen2a1 (Col2a1). In this study we demonstrate that Wif-1 is capable to interfere with CTGF-dependent induction of Acan and Col2a1 gene expression in primary murine chondrocytes. Conversely, CTGF does not interfere with Wif-1-dependent inhibition of Wnt signalling. These results indicate that Wif-1 may be a multifunctional modulator of signalling pathways in the cartilage compartment. J. Cell. Physiol. 227: 2207–2216, 2012. © 2011 Wiley Periodicals, Inc.

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