1. Developmental Biology
  2. Stem Cells and Regenerative Medicine
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A distinct transition from cell growth to physiological homeostasis in the tendon

  1. Mor Grinstein
  2. Heather L Dingwall
  3. Luke D O'Connor
  4. Ken Zou
  5. Terence Dante Capellini
  6. Jenna Lauren Galloway  Is a corresponding author
  1. Massachusetts General Hospital, Harvard Medical School, United States
  2. Harvard University, United States
Research Article
  • Cited 4
  • Views 1,472
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Cite this article as: eLife 2019;8:e48689 doi: 10.7554/eLife.48689

Abstract

Changes in cell proliferation define transitions from tissue growth to physiological homeostasis. In tendons, a highly organized extracellular matrix undergoes significant postnatal expansion to drive growth, but once formed, it appears to undergo little turnover. However, tendon cell activity during growth and homeostatic maintenance is less well defined. Using complementary methods of genetic H2B-GFP pulse-chase labeling and BrdU incorporation in mice, we show significant postnatal tendon cell proliferation, correlating with longitudinal Achilles tendon growth. Around day 21, there is a transition in cell turnover with a significant decline in proliferation. After this time, we find low amounts of homeostatic tendon cell proliferation from 3 to 20 months. These results demonstrate that tendons harbor significant postnatal mitotic activity, and limited, but detectable activity in adult and aged stages. It also points towards the possibility that the adult tendon harbors resident tendon progenitor populations, which would have important therapeutic implications.

Article and author information

Author details

  1. Mor Grinstein

    Center for Regenerative Medicine, Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7166-5593
  2. Heather L Dingwall

    Department of Human Evolutionary Biology, Harvard University, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2377-9777
  3. Luke D O'Connor

    Center for Regenerative Medicine, Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Ken Zou

    Center for Regenerative Medicine, Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Terence Dante Capellini

    Department of Human Evolutionary Biology, Harvard University, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3842-8478
  6. Jenna Lauren Galloway

    Center for Regenerative Medicine, Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, United States
    For correspondence
    JGALLOWAY@mgh.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3792-3290

Funding

National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR071554)

  • Mor Grinstein
  • Heather L Dingwall
  • Ken Zou
  • Terence Dante Capellini
  • Jenna Lauren Galloway

National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR072294)

  • Jenna Lauren Galloway

American Federation for Aging Research

  • Jenna Lauren Galloway

Harvard Stem Cell Institute

  • Jenna Lauren Galloway

Human Frontier Science Program (Fellowship)

  • Mor Grinstein

Milton Fund

  • Terence Dante Capellini

Harvard University Dean's Competitive Fund

  • Terence Dante Capellini

National Science Foundation (Predoctoral fellowship)

  • Heather L Dingwall

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed according to our protocol approved by the Massachusetts General Hospital Institutional Animal Care and Use Committee (IACUC: 2013N000062), and adheres to the recommendations in the Guide for the Care and Use of Laboratory Animals of the NIH.

Reviewing Editor

  1. Clifford J Rosen, Maine Medical Center Research Institute, United States

Publication history

  1. Received: May 22, 2019
  2. Accepted: September 18, 2019
  3. Accepted Manuscript published: September 19, 2019 (version 1)
  4. Version of Record published: October 14, 2019 (version 2)

Copyright

© 2019, Grinstein 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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