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 avisTidsskriftartikelForskningpeer review

    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.

    OriginalsprogEngelsk
    Artikelnummere58184
    TidsskrifteLife
    Vol/bind9
    Sider (fra-til)1-19
    Antal sider19
    ISSN2050-084X
    DOI
    StatusUdgivet - dec. 2020

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