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The role of extracellular matrix phosphorylation on energy dissipation in bone

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 hyp...

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Autores principales: Bailey, Stacyann, Sroga, Grazyna E, Hoac, Betty, Katsamenis, Orestis L, Wang, Zehai, Bouropoulos, Nikolaos, McKee, Marc D, Sørensen, Esben S, Thurner, Philipp J, Vashishth, Deepak
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746230/
https://www.ncbi.nlm.nih.gov/pubmed/33295868
http://dx.doi.org/10.7554/eLife.58184
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author Bailey, Stacyann
Sroga, Grazyna E
Hoac, Betty
Katsamenis, Orestis L
Wang, Zehai
Bouropoulos, Nikolaos
McKee, Marc D
Sørensen, Esben S
Thurner, Philipp J
Vashishth, Deepak
author_facet Bailey, Stacyann
Sroga, Grazyna E
Hoac, Betty
Katsamenis, Orestis L
Wang, Zehai
Bouropoulos, Nikolaos
McKee, Marc D
Sørensen, Esben S
Thurner, Philipp J
Vashishth, Deepak
author_sort Bailey, Stacyann
collection PubMed
description 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, and likely 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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spelling pubmed-77462302020-12-21 The role of extracellular matrix phosphorylation on energy dissipation in bone Bailey, Stacyann Sroga, Grazyna E Hoac, Betty Katsamenis, Orestis L Wang, Zehai Bouropoulos, Nikolaos McKee, Marc D Sørensen, Esben S Thurner, Philipp J Vashishth, Deepak eLife Medicine 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, and likely 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. eLife Sciences Publications, Ltd 2020-12-09 /pmc/articles/PMC7746230/ /pubmed/33295868 http://dx.doi.org/10.7554/eLife.58184 Text en © 2020, Bailey et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Medicine
Bailey, Stacyann
Sroga, Grazyna E
Hoac, Betty
Katsamenis, Orestis L
Wang, Zehai
Bouropoulos, Nikolaos
McKee, Marc D
Sørensen, Esben S
Thurner, Philipp J
Vashishth, Deepak
The role of extracellular matrix phosphorylation on energy dissipation in bone
title The role of extracellular matrix phosphorylation on energy dissipation in bone
title_full The role of extracellular matrix phosphorylation on energy dissipation in bone
title_fullStr The role of extracellular matrix phosphorylation on energy dissipation in bone
title_full_unstemmed The role of extracellular matrix phosphorylation on energy dissipation in bone
title_short The role of extracellular matrix phosphorylation on energy dissipation in bone
title_sort role of extracellular matrix phosphorylation on energy dissipation in bone
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746230/
https://www.ncbi.nlm.nih.gov/pubmed/33295868
http://dx.doi.org/10.7554/eLife.58184
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