The role of extracellular matrix phosphorylation on energy dissipation in bone

Stacyann Bailey; Grazyna E Sroga; Betty Hoac; Orestis L Katsamenis; Zehai Wang; Nikolaos Bouropoulos; Marc D McKee; Esben S Sørensen; Philipp J Thurner; Deepak Vashishth

doi:10.7554/eLife.58184

The role of extracellular matrix phosphorylation on energy dissipation in bone

Stacyann Bailey, Grazyna E Sroga, Betty Hoac, Orestis L Katsamenis, Zehai Wang, Nikolaos Bouropoulos, Marc D McKee, Esben S Sørensen, Philipp J Thurner, Deepak Vashishth

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

11 Citationer (Scopus)

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.

Originalsprog	Engelsk
Artikelnummer	e58184
Tidsskrift	eLife
Vol/bind	9
Sider (fra-til)	1-19
Antal sider	19
ISSN	2050-084X
DOI	https://doi.org/10.7554/eLife.58184
Status	Udgivet - dec. 2020

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10.7554/eLife.58184

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title = "The role of extracellular matrix phosphorylation on energy dissipation in bone",

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.",

author = "Stacyann Bailey and Sroga, {Grazyna E} and Betty Hoac and Katsamenis, {Orestis L} and Zehai Wang and Nikolaos Bouropoulos and McKee, {Marc D} and S{\o}rensen, {Esben S} and Thurner, {Philipp J} and Deepak Vashishth",

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doi = "10.7554/eLife.58184",

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T1 - The role of extracellular matrix phosphorylation on energy dissipation in bone

AU - Bailey, Stacyann

AU - Sroga, Grazyna E

AU - Hoac, Betty

AU - Katsamenis, Orestis L

AU - Wang, Zehai

AU - Bouropoulos, Nikolaos

AU - McKee, Marc D

AU - Sørensen, Esben S

AU - Thurner, Philipp J

AU - Vashishth, Deepak

PY - 2020/12

Y1 - 2020/12

N2 - 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.

AB - 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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U2 - 10.7554/eLife.58184

DO - 10.7554/eLife.58184

M3 - Journal article

C2 - 33295868

SN - 2050-084X

VL - 9

SP - 1

EP - 19

JO - eLife

JF - eLife

M1 - e58184

ER -

The role of extracellular matrix phosphorylation on energy dissipation in bone

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