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http://purl.uniprot.org/citations/27237608http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/27237608http://www.w3.org/2000/01/rdf-schema#comment"Equilibrative nucleoside transporter 1 (ENT1) mediates passage of adenosine across the plasma membrane. We reported previously that mice lacking ENT1 (ENT1(-/-)) exhibit progressive ectopic mineralization of spinal tissues resembling diffuse idiopathic skeletal hyperostosis (DISH) in humans. Here, we investigated mechanisms underlying aberrant mineralization in ENT1(-/-) mice. Micro-CT revealed ectopic mineralization of spinal tissues in both male and female ENT1(-/-) mice, involving the annulus fibrosus of the intervertebral discs (IVDs) of older mice. IVDs were isolated from wild-type and ENT1(-/-) mice at 2months of age (prior to disc mineralization), 4, and 6months of age (disc mineralization present) and processed for real-time PCR, cell isolation, or histology. Relative to the expression of ENTs in other tissues, ENT1 was the primary nucleoside transporter expressed in wild-type IVDs and mediated the functional uptake of [(3)H]2-chloroadenosine by annulus fibrosus cells. No differences in candidate gene expression were detected in IVDs from ENT1(-/-) and wild-type mice at 2 or 4months of age. However, at 6months of age, expression of genes that inhibit biomineralization Mgp, Enpp1, Ank, and Spp1 were reduced in IVDs from ENT1(-/-) mice. To assess whether changes detected in ENT1(-/-) mice were cell autonomous, annulus fibrosus cell cultures were established. Compared to wild-type cells, cells isolated from ENT1(-/-) IVDs at 2 or 6months of age demonstrated greater activity of alkaline phosphatase, a promoter of biomineralization. Cells from 2-month-old ENT1(-/-) mice also showed greater mineralization than wild-type. Interestingly, altered localization of alkaline phosphatase activity was detected in the inner annulus fibrosus of ENT1(-/-) mice in vivo. Alkaline phosphatase activity, together with the marked reduction in mineralization inhibitors, is consistent with the mineralization of IVDs seen in ENT1(-/-) mice at older ages. These findings establish that both cell-autonomous and systemic mechanisms contribute to ectopic mineralization in ENT1(-/-) mice."xsd:string
http://purl.uniprot.org/citations/27237608http://purl.org/dc/terms/identifier"doi:10.1016/j.bone.2016.05.008"xsd:string
http://purl.uniprot.org/citations/27237608http://purl.uniprot.org/core/author"Dixon S.J."xsd:string
http://purl.uniprot.org/citations/27237608http://purl.uniprot.org/core/author"Hammond J.R."xsd:string
http://purl.uniprot.org/citations/27237608http://purl.uniprot.org/core/author"Seguin C.A."xsd:string
http://purl.uniprot.org/citations/27237608http://purl.uniprot.org/core/author"Ii H."xsd:string
http://purl.uniprot.org/citations/27237608http://purl.uniprot.org/core/author"Holdsworth D.W."xsd:string
http://purl.uniprot.org/citations/27237608http://purl.uniprot.org/core/author"Quinonez D."xsd:string
http://purl.uniprot.org/citations/27237608http://purl.uniprot.org/core/author"Warraich S."xsd:string
http://purl.uniprot.org/citations/27237608http://purl.uniprot.org/core/author"Tenn N."xsd:string
http://purl.uniprot.org/citations/27237608http://purl.uniprot.org/core/date"2016"xsd:gYear
http://purl.uniprot.org/citations/27237608http://purl.uniprot.org/core/name"Bone"xsd:string
http://purl.uniprot.org/citations/27237608http://purl.uniprot.org/core/pages"37-49"xsd:string
http://purl.uniprot.org/citations/27237608http://purl.uniprot.org/core/title"Disruption of biomineralization pathways in spinal tissues of a mouse model of diffuse idiopathic skeletal hyperostosis."xsd:string
http://purl.uniprot.org/citations/27237608http://purl.uniprot.org/core/volume"90"xsd:string
http://purl.uniprot.org/citations/27237608http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/27237608
http://purl.uniprot.org/citations/27237608http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/27237608
http://purl.uniprot.org/uniprot/#_E9PZV0-mappedCitation-27237608http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/27237608
http://purl.uniprot.org/uniprot/#_E9Q0Q5-mappedCitation-27237608http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/27237608
http://purl.uniprot.org/uniprot/#_E9Q7R8-mappedCitation-27237608http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/27237608
http://purl.uniprot.org/uniprot/#_A8VP81-mappedCitation-27237608http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/27237608
http://purl.uniprot.org/uniprot/#_E9Q221-mappedCitation-27237608http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/27237608
http://purl.uniprot.org/uniprot/#_E9PWY7-mappedCitation-27237608http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/27237608
http://purl.uniprot.org/uniprot/#_E9PXM6-mappedCitation-27237608http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/27237608