Cargando…
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...
Autores principales: | , , , , , , , , , |
---|---|
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 |
_version_ | 1783624754363629568 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7746230 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT baileystacyann theroleofextracellularmatrixphosphorylationonenergydissipationinbone AT srogagrazynae theroleofextracellularmatrixphosphorylationonenergydissipationinbone AT hoacbetty theroleofextracellularmatrixphosphorylationonenergydissipationinbone AT katsamenisorestisl theroleofextracellularmatrixphosphorylationonenergydissipationinbone AT wangzehai theroleofextracellularmatrixphosphorylationonenergydissipationinbone AT bouropoulosnikolaos theroleofextracellularmatrixphosphorylationonenergydissipationinbone AT mckeemarcd theroleofextracellularmatrixphosphorylationonenergydissipationinbone AT sørensenesbens theroleofextracellularmatrixphosphorylationonenergydissipationinbone AT thurnerphilippj theroleofextracellularmatrixphosphorylationonenergydissipationinbone AT vashishthdeepak theroleofextracellularmatrixphosphorylationonenergydissipationinbone AT baileystacyann roleofextracellularmatrixphosphorylationonenergydissipationinbone AT srogagrazynae roleofextracellularmatrixphosphorylationonenergydissipationinbone AT hoacbetty roleofextracellularmatrixphosphorylationonenergydissipationinbone AT katsamenisorestisl roleofextracellularmatrixphosphorylationonenergydissipationinbone AT wangzehai roleofextracellularmatrixphosphorylationonenergydissipationinbone AT bouropoulosnikolaos roleofextracellularmatrixphosphorylationonenergydissipationinbone AT mckeemarcd roleofextracellularmatrixphosphorylationonenergydissipationinbone AT sørensenesbens roleofextracellularmatrixphosphorylationonenergydissipationinbone AT thurnerphilippj roleofextracellularmatrixphosphorylationonenergydissipationinbone AT vashishthdeepak roleofextracellularmatrixphosphorylationonenergydissipationinbone |