Vitamin-D receptor agonist calcitriol reduces calcification in vitro through selective upregulation of SLC20A2 but not SLC20A1 or XPR1

Vitamin D deficiency (hypovitaminosis D) causes osteomalacia and poor long bone mineralization. In apparent contrast, hypovitaminosis D has been reported in patients with primary brain calcifications (“Fahr’s disease”). We evaluated the expression of two phosphate transporters which we have found to...

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Bibliographic Details
Published in:Scientific reports 2016-05, Vol.6 (1), p.25802-25802, Article 25802
Main Authors: Keasey, M. P., Lemos, R. R., Hagg, T., Oliveira, J. R. M.
Format: Article
Language:English
Subjects:
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Calcification
Calcitriol
CRISPR
Gene expression
Humanities and Social Sciences
Long bone
Mineralization
multidisciplinary
Osteomalacia
Osteosarcoma
Phosphate transporter
Science
Vitamin D
Vitamin deficiency
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Summary:Vitamin D deficiency (hypovitaminosis D) causes osteomalacia and poor long bone mineralization. In apparent contrast, hypovitaminosis D has been reported in patients with primary brain calcifications (“Fahr’s disease”). We evaluated the expression of two phosphate transporters which we have found to be associated with primary brain calcification ( SLC20A2 , whose promoter has a predicted vitamin D receptor binding site and XPR1 ) and one unassociated ( SLC20A1 ), in an in vitro model of calcification. Expression of all three genes was significantly decreased in calcifying human bone osteosarcoma (SaOs-2) cells. Further, we confirmed that vitamin D (calcitriol) reduced calcification as measured by Alizarin Red staining. Cells incubated with calcitriol under calcifying conditions specifically maintained expression of the phosphate transporter SLC20A2 at higher levels relative to controls, by RT-qPCR. Neither SLC20A1 nor XPR1 were affected by calcitriol treatment and remained suppressed. Critically, knockdown of SLC20A2 gene and protein with CRISPR technology in SaOs2 cells significantly ablated vitamin D mediated inhibition of calcification. This study elucidates the mechanistic importance of SLC20A2 in suppressing the calcification process. It also suggests that vitamin D might be used to regulate SLC20A2 gene expression, as well as reduce brain calcification which occurs in Fahr’s disease and normal aging.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep25802