1. Developmental Biology
  2. Evolutionary Biology
Download icon

Secondary ossification center induces and protects growth plate structure

  1. Meng Xie
  2. Pavel Gol'din
  3. Anna Nele Herdina
  4. Jordi Estefa
  5. Ekaterina V Medvedeva
  6. Lei Li
  7. Phillip T Newton
  8. Svetlana Kotova
  9. Boris Shavkuta
  10. Aditya Saxena
  11. Lauren T Shumate
  12. Brian D Metscher
  13. Karl Großschmidt
  14. Shigeki Nishimori
  15. Anastasia Akovantseva
  16. Anna P Usanova
  17. Anastasiia D Kurenkova
  18. Anoop Kumar
  19. Irene Linares Arregui
  20. Paul Tafforeau
  21. Kaj Fried
  22. Mattias Carlström
  23. András Simon
  24. Christian Gasser
  25. Henry M Kronenberg
  26. Murat Bastepe
  27. Kimberly L Cooper
  28. Peter Timashev
  29. Sophie Sanchez
  30. Igor Adameyko
  31. Anders Eriksson
  32. Andrei S Chagin  Is a corresponding author
  1. Karolinska Institutet, Sweden
  2. Schmalhausen Institute of Zoology of NAS of Ukraine, Ukraine
  3. Uppsala University, Evolutionary Biology Centre, Sweden
  4. Sechenov University, Russian Federation
  5. University of California San Diego, United States
  6. Massachusetts General Hospital and Harvard Medical School, United States
  7. University of Vienna, Austria
  8. Medical University of Vienna, Austria
  9. KTH Royal Institute of Technology, Sweden
  10. European Synchrotron Radiation Facility, France
  11. Univeristy of California, San Diego, United States
Research Article
  • Cited 1
  • Views 1,626
  • Annotations
Cite this article as: eLife 2020;9:e55212 doi: 10.7554/eLife.55212

Abstract

Growth plate and articular cartilage constitute a single anatomical entity early in development, but later separate into two distinct structures by the secondary ossification center (SOC). The reason for such separation remains unknown. We found that evolutionarily SOC appears in animals conquering the land - amniotes. Analysis of ossification pattern in mammals with specialized extremities (whales, bats, jerboa) revealed that SOC development correlates with the extent of mechanical loads. Mathematical modelling revealed that SOC reduces mechanical stress within the growth plate. Functional experiments revealed high vulnerability of hypertrophic chondrocytes to mechanical stress and showed that SOC protects these cells from apoptosis caused by extensive loading. Atomic force microscopy showed that hypertrophic chondrocytes are the least mechanically stiff cells within the growth plate. Altogether, these findings suggest that SOC has evolved to protect the hypertrophic chondrocytes from the high mechanical stress encountered in the terrestrial environment.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Meng Xie

    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  2. Pavel Gol'din

    Department of Evolutionary Morphology, Schmalhausen Institute of Zoology of NAS of Ukraine, Kiev, Ukraine
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6118-1384
  3. Anna Nele Herdina

    Department of Physiology and Pharmacology, Karolinska Institutet, Solna, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  4. Jordi Estefa

    Organismal Biology, Uppsala University, Evolutionary Biology Centre, Uppsala, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  5. Ekaterina V Medvedeva

    Institute for Regenerative Medicine, Sechenov University, Moscow, Russian Federation
    Competing interests
    The authors declare that no competing interests exist.
  6. Lei Li

    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  7. Phillip T Newton

    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  8. Svetlana Kotova

    Institute for Regenerative Medicine, Sechenov University, Moscow, Russian Federation
    Competing interests
    The authors declare that no competing interests exist.
  9. Boris Shavkuta

    Institute for Regenerative Medicine, Sechenov University, Moscow, Russian Federation
    Competing interests
    The authors declare that no competing interests exist.
  10. Aditya Saxena

    Division of Biological Sciences, University of California San Diego, San Diego, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Lauren T Shumate

    Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Brian D Metscher

    Department of Theoretical Biology, University of Vienna, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6514-4406
  13. Karl Großschmidt

    Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  14. Shigeki Nishimori

    Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  15. Anastasia Akovantseva

    Institute for Regenerative Medicine, Sechenov University, Moscow, Russian Federation
    Competing interests
    The authors declare that no competing interests exist.
  16. Anna P Usanova

    Institute for Regenerative Medicine, Sechenov University, Moscow, Russian Federation
    Competing interests
    The authors declare that no competing interests exist.
  17. Anastasiia D Kurenkova

    Institute for Regenerative Medicine, Sechenov University, Moscow, Russian Federation
    Competing interests
    The authors declare that no competing interests exist.
  18. Anoop Kumar

    Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  19. Irene Linares Arregui

    Department of Solid Mechanics, KTH Royal Institute of Technology, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  20. Paul Tafforeau

    SoM, European Synchrotron Radiation Facility, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5962-1683
  21. Kaj Fried

    Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  22. Mattias Carlström

    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  23. András Simon

    Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1018-1891
  24. Christian Gasser

    Department of Solid Mechanics, KTH Royal Institute of Technology, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  25. Henry M Kronenberg

    Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  26. Murat Bastepe

    Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  27. Kimberly L Cooper

    Division of Biological Sciences, Section of Cellular and Developmental Biology, Univeristy of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5892-8838
  28. Peter Timashev

    Institute for Regenerative Medicine, Sechenov University, Moscow, Russian Federation
    Competing interests
    The authors declare that no competing interests exist.
  29. Sophie Sanchez

    Organismal Biology, Uppsala University, Evolutionary Biology Centre, Uppsala, Sweden
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3611-6836
  30. Igor Adameyko

    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5471-0356
  31. Anders Eriksson

    Department of Mechanics, KTH Royal Institute of Technology, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  32. Andrei S Chagin

    Department of Physiology and Pharmacology, Karolinska Institutet, Solna, Sweden
    For correspondence
    andrei.chagin@ki.se
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2696-5850

Funding

EMBO

  • Meng Xie
  • Igor Adameyko

Svenska Forskningsrådet Formas

  • Sophie Sanchez
  • Igor Adameyko
  • Andrei S Chagin

Russian Science Foundation

  • Peter Timashev

Stiftelsen Frimurare Barnhuset i Stockholm

  • Meng Xie
  • Phillip T Newton

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 animal experiments were pre-approved by the Ethical Committee on Animal Experiments (N5/16, N187/15, 9091-2018, Stockholm North Committee/ Norra Djurförsöksetiska Nämnden), the Institutional Animal Care and Use Committee of the Massachusetts General Hospital (Protocols #: 2005N000094 and 2004N000176) or the University of California San Diego (D16-00020) and conducted in accordance with the provisions and guidelines for animal experimentation formulated by the Swedish Animal Agency. Animal experiments involving limb unloading, AFM and nanoindentation were pre-approved by the Ethics Committee of the Sechenov First State Moscow Medical University (No. 07-17 from 13.09.2017, Moscow, Russia).

Reviewing Editor

  1. Xu Cao, Johns Hopkins University School of Medicine, United States

Publication history

  1. Received: January 16, 2020
  2. Accepted: October 9, 2020
  3. Accepted Manuscript published: October 16, 2020 (version 1)
  4. Version of Record published: October 22, 2020 (version 2)

Copyright

© 2020, Xie 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.

Metrics

  • 1,626
    Page views
  • 159
    Downloads
  • 1
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Developmental Biology
    Sounak Sahu et al.
    Short Report Updated

    Mechanical stress during cell migration may be a previously unappreciated source of genome instability, but the extent to which this happens in any animal in vivo remains unknown. We consider an in vivo system where the adult stem cells of planarian flatworms are required to migrate to a distal wound site. We observe a relationship between adult stem cell migration and ongoing DNA damage and repair during tissue regeneration. Migrating planarian stem cells undergo changes in nuclear shape and exhibit increased levels of DNA damage. Increased DNA damage levels reduce once stem cells reach the wound site. Stem cells in which DNA damage is induced prior to wounding take longer to initiate migration and migrating stem cell populations are more sensitive to further DNA damage than stationary stem cells. RNAi-mediated knockdown of DNA repair pathway components blocks normal stem cell migration, confirming that active DNA repair pathways are required to allow successful migration to a distal wound site. Together these findings provide evidence that levels of migration-coupled-DNA-damage are significant in adult stem cells and that ongoing migration requires DNA repair mechanisms. Our findings reveal that migration of normal stem cells in vivo represents an unappreciated source of damage, which could be a significant source of mutations in animals during development or during long-term tissue homeostasis.

    1. Developmental Biology
    2. Plant Biology
    Elvira Hernandez-Lagana et al.
    Research Article

    In multicellular organisms, sexual reproduction requires the separation of the germline from the soma. In flowering plants, the female germline precursor differentiates as a single spore mother cell (SMC) as the ovule primordium forms. Here, we explored how organ growth contributes to SMC differentiation. We generated 92 annotated 3D images at cellular resolution in Arabidopsis. We identified the spatio-temporal pattern of cell division that acts in a domain-specific manner as the primordium forms. Tissue growth models uncovered plausible morphogenetic principles involving a spatially confined growth signal, differential mechanical properties, and cell growth anisotropy. Our analysis revealed that SMC characteristics first arise in more than one cell but SMC fate becomes progressively restricted to a single cell during organ growth. Altered primordium geometry coincided with a delay in the fate restriction process in katanin mutants. Altogether, our study suggests that tissue geometry channels reproductive cell fate in the Arabidopsis ovule primordium.