Scleraxis-lineage cell depletion improves tendon healing and disrupts adult tendon homeostasis

Abstract

Despite the requirement for Scleraxis-lineage (ScxLin) cells during tendon development, the function of ScxLin cells during adult tendon repair, post-natal growth, and adult homeostasis have not been defined. Therefore, we inducibly depleted ScxLin cells (ScxLinDTR) prior to tendon injury and repair surgery and hypothesized that ScxLinDTR mice would exhibit functionally deficient healing compared to wildtype littermates. Surprisingly, depletion of ScxLin cells resulted in increased biomechanical properties without impairments in gliding function at 28 days post-repair, indicative of regeneration. RNA sequencing of day 28 post-repair tendons highlighted differences in matrix-related genes, cell motility, cytoskeletal organization, and metabolism. We also utilized ScxLinDTR mice to define the effects on post-natal tendon growth and adult tendon homeostasis and discovered that adult ScxLin cell depletion resulted in altered tendon collagen fibril diameter, density, and dispersion. Collectively, these findings enhance our fundamental understanding of tendon cell localization, function, and fate during healing, growth, and homeostasis.

Data availability

Sequencing data have been deposited in GEO under accession code GSE156157. All other data generated during this study are included in the manuscript and supporting files.

The following previously published data sets were used

Article and author information

Author details

  1. Katherine T Best

    Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Antonion Korcari

    Center for Musculoskeletal Research, Department of Biomedical Engineering, University of Rochester Medical Center, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Keshia E Mora

    Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Anne EC Nichols

    Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Samantha N Muscat

    Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Emma Knapp

    Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Mark R Buckley

    Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Alayna E Loiselle

    Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, United States
    For correspondence
    alayna_loiselle@urmc.rochester.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7548-6653

Funding

National Institute of Arthritis and Musculoskeletal and Skin Diseases (F31 AR074815)

  • Katherine T Best

National Institute of Arthritis and Musculoskeletal and Skin Diseases (K01AR068386)

  • Alayna E Loiselle

National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR073169)

  • Alayna E Loiselle

National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR070765)

  • Mark R Buckley

National Institute of Arthritis and Musculoskeletal and Skin Diseases (T32 AR076950)

  • Anne EC Nichols

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

Reviewing Editor

  1. Mone Zaidi, Icahn School of Medicine at Mount Sinai, United States

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approval by the University Committee on Animal Resources (UCAR) for protocols #2014-004E and 2017-030 at the University of Rochester. All surgery was performed under ketamine anesthesia, and every effort was made to minimize suffering.

Version history

  1. Received: August 17, 2020
  2. Accepted: January 21, 2021
  3. Accepted Manuscript published: January 22, 2021 (version 1)
  4. Version of Record published: February 1, 2021 (version 2)

Copyright

© 2021, Best 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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  1. Katherine T Best
  2. Antonion Korcari
  3. Keshia E Mora
  4. Anne EC Nichols
  5. Samantha N Muscat
  6. Emma Knapp
  7. Mark R Buckley
  8. Alayna E Loiselle
(2021)
Scleraxis-lineage cell depletion improves tendon healing and disrupts adult tendon homeostasis
eLife 10:e62203.
https://doi.org/10.7554/eLife.62203

Share this article

https://doi.org/10.7554/eLife.62203

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