1. Developmental Biology
  2. Stem Cells and Regenerative Medicine
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TGFβ signaling is required for tenocyte recruitment and functional neonatal tendon regeneration

  1. Deepak A Kaji
  2. Kristen L Howell
  3. Zerina Balic
  4. Dirk Hubmacher
  5. Alice H Huang  Is a corresponding author
  1. Icahn School of Medicine at Mount Sinai, United States
Research Article
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Cite this article as: eLife 2020;9:e51779 doi: 10.7554/eLife.51779

Abstract

Tendon injuries are common with poor healing potential. The paucity of therapies for tendon injuries is due to our limited understanding of the cells and molecular pathways that drive tendon regeneration. Using a mouse model of neonatal tendon regeneration, we identified TGFβ signaling as a major molecular pathway that drives neonatal tendon regeneration. Through targeted gene deletion, small molecule inhibition, and lineage tracing, we elucidated TGFβ-dependent and  TGFβ-independent mechanisms underlying tendon regeneration. Importantly, functional recovery depended on canonical TGFβ signaling and loss of function is due to impaired tenogenic cell recruitment from both Scleraxis-lineage and non-Scleraxis-lineage sources.  We show that TGFβ signaling is directly required in neonatal tenocytes for recruitment and that TGFβ ligand is positively regulated in tendons. Collectively, these results show a functional role for canonical TGFβ signaling in tendon regeneration and offer new insights toward the divergent cellular activities that distinguish regenerative vs fibrotic healing.

Article and author information

Author details

  1. Deepak A Kaji

    Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Kristen L Howell

    Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Zerina Balic

    Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Dirk Hubmacher

    Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Alice H Huang

    Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, United States
    For correspondence
    alice.huang@mssm.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5037-6829

Funding

National Institutes of Health (R01AR069537)

  • Alice H Huang

National Institutes of Health (F31AR073626)

  • Deepak A Kaji

National Institutes of Health (R01AR070748)

  • Dirk Hubmacher

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 in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health and all procedures approved by the institutional animal care and use committee (IACUC) at Mount Sinai (IACUC-2014-0031).

Reviewing Editor

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

Publication history

  1. Received: September 11, 2019
  2. Accepted: June 4, 2020
  3. Accepted Manuscript published: June 5, 2020 (version 1)
  4. Version of Record published: June 29, 2020 (version 2)

Copyright

© 2020, Kaji 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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