title: Wif-1 is expressed at cartilage-mesenchyme interfaces and impedes Wnt3a-mediated inhibition of chondrogenesis.
abstract: 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.
authors.affiliation: Department of Experimental Medicine I, Nikolaus-Fiebiger Center of Molecular Medicine, University of Erlangen-Nuremberg, Germany.
authors.forename: Cordula
authors.initials: C
authors.lastname: Surmann-Schmitt
authors.forename: Nathalie
authors.initials: N
authors.lastname: Widmann
authors.forename: Uwe
authors.initials: U
authors.lastname: Dietz
authors.forename: Bernhard
authors.initials: B
authors.lastname: Saeger
authors.forename: Nicole
authors.initials: N
authors.lastname: Eitzinger
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Marianne
authors.initials: M
authors.lastname: Rattel
authors.forename: Richard
authors.initials: R
authors.lastname: Latham
authors.forename: Christine
authors.initials: C
authors.lastname: Hartmann
authors.forename: Helga
authors.initials: H
authors.lastname: von der Mark
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
authors.forename: Klaus
authors.initials: K
authors.lastname: von der Mark
authors.forename: Michael
authors.initials: M
authors.lastname: Stock
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000831:Animals, Newborn; D002356:Cartilage / Q000196:embryology* / Q000378:metabolism*; D049109:Cell Proliferation; D002642:Chick Embryo; D020219:Chondrogenesis / Q000235:genetics; D047108:Embryonic Development; D004838:Epiphyses / Q000196:embryology / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005121:Extremities / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D018878:Limb Buds / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D051379:Mice; D011485:Protein Binding; D015398:Signal Transduction; D046509:Tissue Culture Techniques; D051153:Wnt Proteins / Q000378:metabolism*; D060508:Wnt3 Protein; D060509:Wnt3A Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016326:Extracellular Matrix Proteins; D036341:Intercellular Signaling Peptides and Proteins; C118544:Wif1 protein, mouse; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse