Osteoclast-mediated resorption primes the skeleton for successful integration during axolotl limb regeneration

  1. Camilo Riquelme-Guzmán
  2. Stephanie L Tsai
  3. Karen Carreon Paz
  4. Congtin Nguyen
  5. David Oriola
  6. Maritta Schuez
  7. Jan Brugués
  8. Joshua D Currie
  9. Tatiana Sandoval-Guzman  Is a corresponding author
  1. Technische Universität Dresden, Germany
  2. Harvard University, United States
  3. European Molecular Biology Laboratory, Spain
  4. Max Planck Institute of Molecular Cell Biology and Genetics, Germany
  5. Wake Forest University, United States

Abstract

Early events during axolotl limb regeneration include an immune response and the formation of a wound epithelium. These events are linked to a clearance of damaged tissue prior to blastema formation and regeneration of the missing structures. Here, we report the resorption of calcified skeletal tissue as an active, cell-driven and highly regulated event. This process, carried out by osteoclasts, is essential for a successful integration of the newly formed skeleton. Indeed, the extent of resorption is directly correlated with the integration efficiency and treatment with zoledronic acid resulted in osteoclast function inhibition and failed tissue integration. Moreover, we identified the wound epithelium as a regulator of skeletal resorption, likely releasing signals involved in recruitment/differentiation of osteoclasts. Finally, we reported a correlation between resorption and blastema formation, particularly, a coordination of resorption with cartilage condensation. In sum, our results identify resorption as a major event upon amputation, playing a critical role in the overall process of skeletal regeneration.

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No dataset have been generated for this manuscript.

The following previously published data sets were used

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Author details

  1. Camilo Riquelme-Guzmán

    Center for Regenerative Therapies, Technische Universität Dresden, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5126-6584
  2. Stephanie L Tsai

    Department of Stem Cell and Regenerative 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:" 0000-0001-7549-3418
  3. Karen Carreon Paz

    Center for Regenerative Therapies, Technische Universität Dresden, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Congtin Nguyen

    Center for Regenerative Therapies, Technische Universität Dresden, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. David Oriola

    European Molecular Biology Laboratory, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8356-7832
  6. Maritta Schuez

    Center for Regenerative Therapies, Technische Universität Dresden, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Jan Brugués

    Molecular Cell Biology and Genetics, Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6731-4130
  8. Joshua D Currie

    Department of Biology, Wake Forest University, Winston-Salem, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Tatiana Sandoval-Guzman

    Department of Internal Medicine 3, Technische Universität Dresden, Dresden, Germany
    For correspondence
    tatiana.sandoval_guzman@tu-dresden.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1802-5145

Funding

Deutsche Forschungsgemeinschaft (SA 3349/3-1)

  • Camilo Riquelme-Guzmán
  • Tatiana Sandoval-Guzman

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

Ethics

Animal experimentation: All procedures were performed according to the Animal Ethics Committee of the State of Saxony, Germany, and the Institutional Animal Care and Use Committee (IACUC) Guidelines at Harvard University (Protocol 11-32).

Reviewing Editor

  1. Mei Wan, Johns Hopkins University, United States

Publication history

  1. Preprint posted: April 27, 2022 (view preprint)
  2. Received: May 4, 2022
  3. Accepted: October 11, 2022
  4. Accepted Manuscript published: October 11, 2022 (version 1)
  5. Version of Record published: October 19, 2022 (version 2)

Copyright

© 2022, Riquelme-Guzmán 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. Camilo Riquelme-Guzmán
  2. Stephanie L Tsai
  3. Karen Carreon Paz
  4. Congtin Nguyen
  5. David Oriola
  6. Maritta Schuez
  7. Jan Brugués
  8. Joshua D Currie
  9. Tatiana Sandoval-Guzman
(2022)
Osteoclast-mediated resorption primes the skeleton for successful integration during axolotl limb regeneration
eLife 11:e79966.
https://doi.org/10.7554/eLife.79966

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