Deepak Vashishth's article in eLife

Posted December 9, 2020

An article by Deepak Vashishth's group on "The Role of Extracellular Matrix Phosphorylation on Energy Dissipation in Bone" has been accepted for publication in eLife. The paper is the result of an international collaboration with authors from McGill (Canada), University of Southampton (UK), University of Patras (Greece), Aarhus University (Denmark) and Vienna University of Technology (Austria).  This work launches a new field in bone research as it is shown for the first time and explored mechanistically, how phosphorylation, an enzymatic modification, in bone proteins enhances bone fragility seen in many diseases (hypo- and hyper- phosphatemia, diabetes, cancer) and age.

The article can be found here:

and the abstract is shown below:

"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, 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."