1. Cell Biology
  2. Developmental Biology
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Matrix metalloproteinase 14 is required for fibrous tissue expansion

  1. Susan H Taylor
  2. Ching-Yan Chloé Yeung
  3. Nicholas S Kalson
  4. Yinhui Lu
  5. Paola Zigrino
  6. Tobias Starborg
  7. Stacey Warwood
  8. David F Holmes
  9. Elizabeth G Canty-Laird
  10. Cornelia Mauch
  11. Karl E Kadler  Is a corresponding author
  1. University of Manchester, United Kingdom
  2. University of Cologne, Germany
  3. University of Liverpool, United Kingdom
Research Article
  • Cited 16
  • Views 2,316
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Cite this article as: eLife 2015;4:e09345 doi: 10.7554/eLife.09345

Abstract

Type I collagen-containing fibrils are major structural components of the extracellular matrix of vertebrate tissues, especially tendon, but how they are formed is not fully understood. MMP14 is a potent pericellular collagenase that can cleave type I collagen in vitro. Here we show that tendon development is arrested in Scleraxis-Cre::Mmp14 lox/lox mice that are unable to release collagen fibrils from plasma membrane fibripositors. In contrast to its role in collagen turnover in adult tissue, MMP14 promotes embryonic tissue formation by releasing collagen fibrils from the cell surface. Notably, tendons grow to normal size and collagen fibril release from fibripositors occurs in Col-r/r mice that have a mutated collagen-I that is uncleavable by MMPs. Furthermore, fibronectin (not collagen-I) accumulates in tendons of Mmp14-null mice. We propose a model for cell-regulated collagen fibril assembly during tendon development in which MMP14 cleaves a molecular bridge tethering collagen fibrils to the plasma membrane of fibripositors.

Article and author information

Author details

  1. Susan H Taylor

    Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Ching-Yan Chloé Yeung

    Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Nicholas S Kalson

    Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Yinhui Lu

    Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Paola Zigrino

    Department of Dermatology, Center for Molecular Medicine, University of Cologne, Cologne, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Tobias Starborg

    Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Stacey Warwood

    Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. David F Holmes

    Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Elizabeth G Canty-Laird

    Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  10. Cornelia Mauch

    Department of Dermatology, Center for Molecular Medicine, University of Cologne, Cologne, Germany
    Competing interests
    The authors declare that no competing interests exist.
  11. Karl E Kadler

    Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom
    For correspondence
    karl.kadler@manchester.ac.uk
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: The care and use of all mice in this study was carried out in accordance with UK Home Office regulations, UK Animals (Scientific Procedures) Act of 1986 under the UK Home Office licence (PPL 40/3485). All animals were sacrificed by a Schedule 1 procedure by trained personnel. MMP14 KO mice were as described previously (Zhou et al., 2000). To generate mice in which MMP14 is ablated in tendon-lineage cells, we crossed mice expressing Cre recombinase under the control of Scleraxis (ScxCre; C57BL/6) (Blitz et al., 2013) with mice carrying the floxed exons (exons 2 to 4) of the MMP14 gene (MMP14-floxed; C57BL/6) (Zigrino et al., 2012). MMP13 KO embryos were a generous gift from Zena Werb (Stickens et al., 2004). MMP2 heterozygous mice were imported from RIKEN BioResource Center (GelAKO/RBRC00398; C57) (Itoh et al., 1997) and bred to homozygosity. Col-r/r mice were imported from Jackson Laboratory (B6;129S4-Col1a1tm1Jae/J) (Liu et al., 1995). X-ray analyses were performed as described previously (Yeung et al., 2014).

Reviewing Editor

  1. Robb Krumlauf, Stowers Institute for Medical Research, United States

Publication history

  1. Received: June 10, 2015
  2. Accepted: September 20, 2015
  3. Accepted Manuscript published: September 21, 2015 (version 1)
  4. Version of Record published: October 20, 2015 (version 2)

Copyright

© 2015, Taylor et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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