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Primary Dupuytren’s Disease Cell Interactions with the Extra-cellular Environment: A Link to Disease Progression?

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Dupuytren’s Disease and Related Hyperproliferative Disorders

Abstract

Comparative gene expression analyses of Dupuytren’s disease tissues and unaffected palmar fascia have consistently identified large numbers of gene transcripts that encode extra-cellular matrix molecules. The relevance of a modified extra-cellular matrix to Dupuytren’s disease progression is unclear. In this study, we have tested two hypotheses: (1) that a modified extra-cellular matrix facilitates Dupuytren’s disease cell migration and (2) that Dupuytren’s disease cells modify their extra-cellular matrix to induce adjacent cells to take on disease cell characteristics. Our data suggest that transforming growth factor β1, periostin and a disintegrin and metalloprotease 12, molecules associated with the extra-cellular matrix and upregulated in Dupuytren’s disease, either inhibit or have no discernable effect on three-dimensional migration of primary Dupuytren’s disease cells relative to cells from phenotypically unaffected palmar fascia. In contrast, a collagen substrate conditioned by primary Dupuytren’s disease cells, but not patient-matched control cells, induces rapid β-catenin accumulation in cells from phenotypically unaffected palmar fascia. As upregulated cytoplasmic β-catenin is one of several characteristics that distinguish DD cells from cells of the adjacent palmar fascia, these data support the hypothesis that a modified extra-cellular matrix promotes Dupuytren’s disease progression by inducing fibroblasts resident in the palmar fascia to take on a disease cell phenotype.

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Acknowledgments

We would like to acknowledge Ms Karen Nygard at the Biotron of the University of Western Ontario for her expert assistance with stereomicroscopy. We also acknowledge the Canadian Institutes of Health Research and The Lawson Health Research Institute Internal Research Fund for financial support.

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Authors and Affiliations

  1. Cell and Molecular Biology Laboratory, Hand and Upper Limb Centre, St. Joseph’s Health Care, Lawson Health Research Institute, University of Western Ontario, London, ON, Canada

    Linda Vi & Yan Wu

  2. Departments of Surgery, Physiology and Pharmacology, Medical Biophysics, Cell and Molecular Biology Laboratory, Hand and Upper Limb Centre, St. Joseph’s Health Care, Lawson Health Research Institute, University of Western Ontario, London, ON, Canada

    Bing Siang Gan & David B. O’Gorman

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  1. Linda Vi
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  2. Yan Wu
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  3. Bing Siang Gan
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  4. David B. O’Gorman
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Correspondence to Linda Vi .

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Editors and Affiliations

  1. The Hand Center, S Old Dixie Highway 1002, Jupiter, 33458, Florida, USA

    Charles Eaton

  2. Strahlenzentrum Hamburg, Langenhorner Chaussee 369, Hamburg, 22419, Germany

    M. Heinrich Seegenschmiedt

  3. Manchester Interdisciplinary Biocentre, Plastic & Reconstructive Surgery, University of Manchester, Princess Street 131, Manchester, M1 7DN, United Kingdom

    Ardeshir Bayat

  4. Faculty of Medicine, Dept. of Pathology and Immunology, University of Geneva, Rue Michel-Servet 1, Geneva, 1211, Switzerland

    Giulio Gabbiani

  5. Medical Center, Department of Plastic Surgery, University of Groningen, Hanzeplein 1, Groningen, 9713 GZ, Netherlands

    Paul Werker

  6. Dupuytren e.V., Westerbuchberg 60b, Übersee, 83236, Germany

    Wolfgang Wach

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Vi, L., Wu, Y., Gan, B.S., O’Gorman, D.B. (2012). Primary Dupuytren’s Disease Cell Interactions with the Extra-cellular Environment: A Link to Disease Progression?. In: Eaton, C., Seegenschmiedt, M., Bayat, A., Gabbiani, G., Werker, P., Wach, W. (eds) Dupuytren’s Disease and Related Hyperproliferative Disorders. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-22697-7_19

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  • DOI: https://doi.org/10.1007/978-3-642-22697-7_19

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  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-22696-0

  • Online ISBN: 978-3-642-22697-7

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