Investigating The Mechanism Of Ectopic Mineralization In A Mouse Model Of Diffuse Idiopathic Skeletal Hyperostosis (DISH)

Author

Neil A. Tenn, The University of Western OntarioFollow

Degree

Master of Science

Program

Physiology and Pharmacology

Supervisor

Dr. Cheryle Séguin

2nd Supervisor

Dr. Jeffrey Dixon

Joint Supervisor

Abstract

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^-/- cells. We also characterized differences in the AF cell phenotype between WT and ENT1^-/- mice using transcriptome analysis, revealing the association between activation of cell cycle and B cells with the induction of mineralization. In summary, both cell-autonomous and systemic mechanisms contribute to ectopic mineralization in ENT1^-/- mice, possibly through alterations in ALP distribution and activity.

Recommended Citation

Tenn, Neil A., "Investigating The Mechanism Of Ectopic Mineralization In A Mouse Model Of Diffuse Idiopathic Skeletal Hyperostosis (DISH)" (2015). Electronic Thesis and Dissertation Repository. 2966.
https://ir.lib.uwo.ca/etd/2966