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2018 ; 8
(1
): 2069
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Magnesium prevents vascular calcification in vitro by inhibition of
hydroxyapatite crystal formation
#MMPMID29391410
Ter Braake AD
; Tinnemans PT
; Shanahan CM
; Hoenderop JGJ
; de Baaij JHF
Sci Rep
2018[Feb]; 8
(1
): 2069
PMID29391410
show ga
Magnesium has been shown to effectively prevent vascular calcification associated
with chronic kidney disease. Magnesium has been hypothesized to prevent the
upregulation of osteoblastic genes that potentially drives calcification.
However, extracellular effects of magnesium on hydroxyapatite formation are
largely neglected. This study investigated the effects of magnesium on
intracellular changes associated with transdifferentiation and extracellular
crystal formation. Bovine vascular smooth muscle cells were calcified using
?-glycerophosphate. Transcriptional analysis, alkaline phosphatase activity and
detection of apoptosis were used to identify transdifferentiation. Using X-ray
diffraction and energy dispersive spectroscopy extracellular crystal composition
was investigated. Magnesium prevented calcification in vascular smooth muscle
cells. ?-glycerophosphate increased expression of osteopontin but no other genes
related to calcification. Alkaline phosphatase activity was stable and apoptosis
was only detected after calcification independent of magnesium. Blocking of the
magnesium channel TRPM7 using 2-APB did not abrogate the protective effects of
magnesium. Magnesium prevented the formation of hydroxyapatite, which formed
extensively during ?-glycerophosphate treatment. Magnesium reduced calcium and
phosphate fractions of 68% and 41% extracellular crystals, respectively, without
affecting the fraction of magnesium. This study demonstrates that magnesium
inhibits hydroxyapatite formation in the extracellular space, thereby preventing
calcification of vascular smooth muscle cells.