A Bioinformatics Approach to Understanding the Pathogenesis of Ectopic Spine Calcification
Abstract
This study used mice lacking equilibrative nucleoside transporter 1 (ENT1-/-) as a preclinical model to study pathogenesis of ectopic spine mineralization in diffuse idiopathic skeletal hyperostosis (DISH). We hypothesized that mineralization of the annulus fibrosus (AF), was driven by dysregulation of cellular processes and pathways associated with apoptosis, S100A9 proteins, the PI3K-Akt pathway, and lipid metabolism. Target pathways and processes were assessed using in situ localization and quantitative analyses. Metabolomic analysis of AF and plasma data was conducted to identify altered metabolites. Results demonstrate increased caspase-3 activity in the AF of ENT1-/- mice at both timepoints and decreased S100A9 in the AF of ENT1-/- mice at 2 months. PI3K and Akt proteins levels were decreased in male and female ENT1-/- mice at 6 months. Metabolomic analyses of AF and plasma suggested dysregulation in lipid metabolism and a decrease in betaine and choline levels, which may be linked to ectopic mineralization.