Mineral content of the maternal diet influences ectopic mineralization in offspring of Abcc6^−/− mice

Abstract

Abbreviations: ACDC, arterial calcification due to CD73 deficiency; GACI, generalized arterial calcification of infancy; PXE, pseudoxanthoma elasticum.Ectopic mineralization disorders inflicting the connective tissues display a spectrum of severity, some developing in utero and being diagnosed by prenatal ultrasound. This study was designed to test the hypothesis that the mineral content of maternal diet can influence the mineralization in the offspring. Pregnant Abcc6 ¡/¡ mice, on 2 different strain backgrounds, were maintained either on normal rodent diet or on "acceleration diet," rich in phosphate and low in magnesium, which has been previously shown to enhance the mineralization processes. The offspring were examined for mineralization by histopathology of various tissues and quantitated by chemical assay of calcium. The ectopic mineralization in the dermal sheath of vibrissae, a progressive biomarker of the overall mineralization, was readily detectable at the age of 4 weeks in the pups whose mothers were on the acceleration diet, while no evidence of mineralization was noted in those on normal diet. The mineralization of the vibrissae progressively increased when examined at 12 weeks of age. There was a significant reduction in urinary calcium and significant increase in urinary phosphorus concentrations both at 4 and 12 weeks of age in mice on the acceleration diet as compared to those on control diet. The results demonstrate that the mineral content of the maternal diet can influence ectopic mineralization in the offspring of mice genetically predisposed to ectopic mineralization (Abcc6 ¡/¡ ). These observations have implications for dietary management of pregnancies in which the fetus is diagnosed by prenatal ultrasound to have an ectopic mineralization disorder.

Plasma PPi Deficiency Is the Major, but Not the Exclusive, Cause of Ectopic Mineralization in an Abcc6 Mouse Model of PXE

“…The onset and extent of mineralization in the vibrissae and other tissues is, however, highly dependent on the mineral composition of the diet. Ectopic mineralization is enhanced in Abcc6 e/e mice when they are placed on an "acceleration diet" enriched in phosphorus and low in magnesium (Jiang and Uitto, 2012;Li et al, 2015). In addition, plasma PPi levels in Abcc6 e/e mice are reduced to approximately 30% of those of wild-type (WT) mice (Jansen et al, 2014).…”

Living inside the box: environmental effects on mouse models of human disease

“…Atherogenesis can be induced by placing the mice on high-fat diets, especially for lines that carry mutations involved in the pathogenesis of this disease ( Chistiakov et al, 2017 ). Diet can modify the onset and severity of disease as well; for example, ectopic soft-tissue mineralization, a feature of pseudoxanthoma elasticum ( Uitto et al, 2014 ) and several related diseases ( Li and Uitto, 2013 ), can be exacerbated when mice are fed an experimental diet high in phosphate and low in magnesium content ( Jiang and Uitto, 2012 ; Li et al, 2015 ). This so-called ‘acceleration diet’ shortens the time the investigated mice require to develop features of pseudoxanthoma elasticum.…”

High magnesium prevents matrix vesicle‐mediated mineralization in human bone marrow‐derived mesenchymal stem cells via mitochondrial pathway and autophagy

“…The presence of high extracellular Mg 2þ prevented the formation of extracellular calcifying matrix and to control the growth of hydroxyapatite crystals (Serre et al, 1998). Ectopic mineralization of connective tissue can be effectively inhibited by magnesium supplementation (Li et al, 2015). In addition, magnesium supplementation alleviates vascular calcification in both rodent and bovine models through restored magnesium channel transient receptor potential melastatin (TRPM7) activity (Louvet et al, 2016).…”