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The role of extracellular matrix phosphorylation on energy dissipation in bone

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  • Stacyann Bailey, Rensselaer Polytech Inst, Rensselaer Polytechnic Institute, Dept Biol Sci
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  • Grazyna E Sroga, Rensselaer Polytech Inst, Rensselaer Polytechnic Institute, Dept Biol Sci
  • ,
  • Betty Hoac, McGill University
  • ,
  • Orestis L Katsamenis, University of Southampton
  • ,
  • Zehai Wang, Rensselaer Polytechnic Institute
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  • Nikolaos Bouropoulos, University of Patras
  • ,
  • Marc D McKee, McGill University
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  • Esben S Sørensen
  • Philipp J Thurner, Vienna University of Technology, Vienna
  • ,
  • Deepak Vashishth, Rensselaer Polytech Inst, Rensselaer Polytechnic Institute, Dept Biol Sci

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.

OriginalsprogEngelsk
Artikelnummere58184
TidsskrifteLife
Vol/bind9
ISSN2050-084X
DOI
StatusUdgivet - dec. 2020

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