The role of extracellular matrix phosphorylation on energy dissipation in bone

  1. Stacyann Bailey
  2. Grazyna E Sroga
  3. Betty Hoac
  4. Orestis L Katsamenis
  5. Zehai Wang
  6. Nikolaos Bouropoulos
  7. Marc D McKee
  8. Esben S Sorensen
  9. Philipp J Thurner
  10. Deepak Vashishth  Is a corresponding author
  1. Rensselaer Polytechnic Institute, United States
  2. McGill University, Canada
  3. University of Southampton, United Kingdom
  4. University of Patras, Greece
  5. Aarhus University, Denmark
  6. Vienna University of Technology, Austria

Abstract

Protein phosphorylation, critical for cellular regulatory mechanisms, is implicated in various diseases. However, it remains unknown whether heterogeneity in phosphorylation of key structural proteins alters tissue integrity and organ function. Here, osteopontin phosphorylation level declined in hypo- and hyper- phosphatemia mouse models exhibiting skeletal deformities. Phosphorylation increased cohesion between osteopontin polymers, and adhesion of osteopontin to hydroxyapatite, enhancing energy dissipation. Fracture toughness, a measure of bone's mechanical competence, increased with ex-vivo phosphorylation of wildtype mouse bones and declined with ex-vivo dephosphorylation. In osteopontin deficient mice, global matrix phosphorylation level was not associated with toughness. Our findings suggest that phosphorylated osteopontin promotes fracture toughness in a dose-dependent manner through increased interfacial bond formation. In the absence of osteopontin, phosphorylation increases electrostatic repulsion, protein alignment, and interfilament distance leading to decreased fracture resistance. These mechanisms may be of importance in other connective tissues, and the key to unraveling cell-matrix interactions in diseases.

Data availability

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

Article and author information

Author details

  1. Stacyann Bailey

    Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9013-2469
  2. Grazyna E Sroga

    Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, United States
    Competing interests
    No competing interests declared.
  3. Betty Hoac

    Faculty of Dentistry, McGill University, Montreal, Canada
    Competing interests
    No competing interests declared.
  4. Orestis L Katsamenis

    Faculty of Engineering and Physical Sciences, University of Southampton, Southampton, United Kingdom
    Competing interests
    No competing interests declared.
  5. Zehai Wang

    Mechanical, Aerospace, and Nuclear Engineering, Rensselaer Polytechnic Institute, Troy, United States
    Competing interests
    No competing interests declared.
  6. Nikolaos Bouropoulos

    Department of Material Science, University of Patras, Patras, Greece
    Competing interests
    No competing interests declared.
  7. Marc D McKee

    Faculty of Dentistry, Department of Anatomy and Cell Biology, Faculty of Medicine, McGill University, Montreal, Canada
    Competing interests
    Marc D McKee, MDM is a member of the FRQS Network for Oral and Bone Health Research, and he holds the Canada Research Chair in Biomineralization as part of the Canada Research Chairs program which contributed to the funding of this work..
  8. Esben S Sorensen

    Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7050-3354
  9. Philipp J Thurner

    Institute of Lightweight Design and Structural Biomechanics, Vienna University of Technology, Vienna, Austria
    Competing interests
    No competing interests declared.
  10. Deepak Vashishth

    Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, United States
    For correspondence
    vashid@rpi.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5712-0167

Funding

National Institutes of Health (AR 49635)

  • Stacyann Bailey
  • Grazyna E Sroga
  • Zehai Wang
  • Deepak Vashishth

Canadian Institutes of Health Research

  • Betty Hoac
  • Marc D McKee

University of Southampton (Doctoral Prize Fellowship)

  • Orestis L Katsamenis

Canada Research Chairs

  • Marc D McKee

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

Reviewing Editor

  1. Cheryl Ackert-Bicknell, University of Colorado, 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 approved institutional animal care and use committee (IACUC) protocols (VAS-001-14) of Rensselaer Polytechnic Institute.

Version history

  1. Received: April 23, 2020
  2. Accepted: December 7, 2020
  3. Accepted Manuscript published: December 9, 2020 (version 1)
  4. Accepted Manuscript updated: December 16, 2020 (version 2)
  5. Version of Record published: December 17, 2020 (version 3)

Copyright

© 2020, Bailey 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. Stacyann Bailey
  2. Grazyna E Sroga
  3. Betty Hoac
  4. Orestis L Katsamenis
  5. Zehai Wang
  6. Nikolaos Bouropoulos
  7. Marc D McKee
  8. Esben S Sorensen
  9. Philipp J Thurner
  10. Deepak Vashishth
(2020)
The role of extracellular matrix phosphorylation on energy dissipation in bone
eLife 9:e58184.
https://doi.org/10.7554/eLife.58184

Share this article

https://doi.org/10.7554/eLife.58184

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