A distinct transition from cell growth to physiological homeostasis in the tendon
- Massachusetts General Hospital, Harvard Medical School, United States
- Harvard University, United States
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.
Data availability
All data generated or analyzed in this study are included in the manuscript and supporting files. Source data and R code have been provided for Figure 4.
Article and author information
Author details
Heather L Dingwall
Terence Dante Capellini
Jenna Lauren Galloway
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.
Reviewing Editor
- Clifford J Rosen, Maine Medical Center Research Institute, United States
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.
Version history
- Received: May 22, 2019
- Accepted: September 18, 2019
- Accepted Manuscript published: September 19, 2019 (version 1)
- 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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A distinct transition from cell growth to physiological homeostasis in the tendon
eLife 8:e48689.
https://doi.org/10.7554/eLife.48689
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