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First published online 15 September 2009
doi: 10.1242/jcs.048926

Journal of Cell Science 122, 3627-3637 (2009)
Published by The Company of Biologists 2009
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Research Article

Wif-1 is expressed at cartilage-mesenchyme interfaces and impedes Wnt3a-mediated inhibition of chondrogenesis

Cordula Surmann-Schmitt1, Nathalie Widmann1, Uwe Dietz1, Bernhard Saeger1,2, Nicole Eitzinger1, Yukio Nakamura3, Marianne Rattel1, Richard Latham4, Christine Hartmann4, Helga von der Mark1, Georg Schett5, Klaus von der Mark1 and Michael Stock1,*

1 Department of Experimental Medicine I, Nikolaus-Fiebiger Center of Molecular Medicine, University of Erlangen-Nuremberg, Germany
2 Institute of Biology I, University of Freiburg, Germany
3 Howard Hughes Medical Institute, Department of Orthopedic Surgery and Genetics, Children's Hospital and Harvard Medical School, Boston, MA, USA
4 Institute of Molecular Pathology, Bohrgasse, Vienna, Austria
5 Department of Internal Medicine 3, Erlangen Medical School, University of Erlangen–Nuremberg, Germany

* Author for correspondence (mstock{at}molmed.uni-erlangen.de)

Accepted 18 July 2009

Wnt factors are involved in the regulation of all steps of cartilage development. The activity of Wnt factors is generally regulated at the extracellular level by factors like the Dkk family, sFRPs, Cerberus and Wnt inhibitory factor 1 (Wif-1). Here we report that Wif-1 is highly expressed at cartilage-mesenchyme interfaces of the early developing skeleton. In fetal and postnatal skeletal development, Wif-1 is expressed in a sharply restricted zone in the upper hyaline layer of epiphyseal and articular cartilage and in trabecular bone. Coimmunoprecipitation and pull-down assays using recombinant Wif-1 and Wnt factors show specific binding of Wif-1 to Wnt3a, Wnt4, Wnt5a, Wnt7a, Wnt9a and Wnt11. Moreover, Wif-1 was able to block Wnt3a-mediated activation of the canonical Wnt signalling pathway. Consequently, Wif-1 impaired growth of mesenchymal precursor cells and neutralised Wnt3a-mediated inhibition of chondrogenesis in micromass cultures of embryonic chick limb-bud cells. These results identify Wif-1 as a novel extracellular Wnt modulator in cartilage biology.

Key words: Wif-1, Wnt signalling, β-catenin, Chondrocyte, Chondrogenesis


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© The Company of Biologists Ltd 2009