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The role of extracellular matrix phosphorylation on energy dissipation in bone

The role of extracellular matrix phosphorylation on energy dissipation in bone
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 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.

2050-084X
Bailey, Stacyann
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Sroga, Grazyna E
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Hoac, Betty
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Katsamenis, Orestis L
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Wang, Zehai
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Bouropoulos, Nikolaos
fadadea1-2aa2-4cd9-a7e5-33ba790cd45f
McKee, Marc D
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Sorenson, Esben S
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Thurner, Philipp J
ab711ddd-784e-48de-aaad-f56aec40f84f
Vashishth, Deepak
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Bailey, Stacyann
7de56183-074a-4ca2-b8d4-20e88c17892c
Sroga, Grazyna E
f782f60f-cb11-4387-b536-c21f02720225
Hoac, Betty
91c3c898-97ff-4e99-b37d-e6354d908f64
Katsamenis, Orestis L
8553e7c3-d860-4b7a-a883-abf6c0c4b438
Wang, Zehai
1d63ab2e-d4df-4dc9-9a2e-77b4a7b2dd96
Bouropoulos, Nikolaos
fadadea1-2aa2-4cd9-a7e5-33ba790cd45f
McKee, Marc D
fe8b47b8-c17e-4ac3-a7b3-85591cc215b6
Sorenson, Esben S
8d49a1c3-2639-4c6f-b636-57321428935a
Thurner, Philipp J
ab711ddd-784e-48de-aaad-f56aec40f84f
Vashishth, Deepak
7fe43949-aed2-4b3b-ba5d-f5529fbf8104

Bailey, Stacyann, Sroga, Grazyna E, Hoac, Betty, Katsamenis, Orestis L, Wang, Zehai, Bouropoulos, Nikolaos, McKee, Marc D, Sorenson, Esben S, Thurner, Philipp J and Vashishth, Deepak (2020) The role of extracellular matrix phosphorylation on energy dissipation in bone. eLife, 9. (doi:10.7554/eLife.58184).

Record type: Article

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, 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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Bailey2020 - The role of extracellular matrix phosphorylation on energy dissipation in bone - Accepted Manuscript
Available under License Creative Commons Attribution.
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e-pub ahead of print date: 9 December 2020
Published date: 9 December 2020
Additional Information: © 2020, Bailey et al.

Identifiers

Local EPrints ID: 445953
URI: http://eprints.soton.ac.uk/id/eprint/445953
ISSN: 2050-084X
PURE UUID: f007963f-8559-4cda-9b78-4802af402d4a
ORCID for Orestis L Katsamenis: ORCID iD orcid.org/0000-0003-4367-4147
ORCID for Philipp J Thurner: ORCID iD orcid.org/0000-0001-7588-9041

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Date deposited: 15 Jan 2021 17:31
Last modified: 28 Apr 2022 02:05

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Contributors

Author: Stacyann Bailey
Author: Grazyna E Sroga
Author: Betty Hoac
Author: Zehai Wang
Author: Nikolaos Bouropoulos
Author: Marc D McKee
Author: Esben S Sorenson
Author: Deepak Vashishth

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