The role of extracellular matrix phosphorylation on energy dissipation in bone
- Rensselaer Polytechnic Institute, United States
- McGill University, Canada
- University of Southampton, United Kingdom
- University of Patras, Greece
- Aarhus University, Denmark
- 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.
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All data generated or analyzed during this study are included in the manuscript and supporting files.
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Author details
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.
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.
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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The role of extracellular matrix phosphorylation on energy dissipation in bone
eLife 9:e58184.
https://doi.org/10.7554/eLife.58184
