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Investigating The Mechanism Of Ectopic Mineralization In A Mouse Model Of Diffuse Idiopathic Skeletal Hyperostosis (Dish), Neil A. Tenn

Electronic Thesis and Dissertation Repository

Equilibrative nucleoside transporter 1 (ENT1) transfers adenosine across plasma membranes. Mice lacking ENT1 (ENT1^-/-) develop pathological calcification of spinal tissues resembling diffuse idiopathic skeletal hyperostosis (DISH) in humans. Our goal was to investigate the mechanism underlying ectopic mineralization in ENT1^-/- mice. We detected aberrant alkaline phosphatase (ALP, promoter of mineralization) activity in the annulus fibrosus (AF) of ENT1^-/- mice. In vitro, AF cells from ENT1^-/- mice exhibited greater ALP activity than cells from wild-type (WT) mice. Inhibition of ENT1 in the presence of extracellular adenosine modeled in WT cells the phenotype of ENT1 …