Pluto Bioinformatics

GSE136593: RNA sequencing of aortic tissue of Klotho knock-out mice treated with a minimal and a high magnesium diet

Bulk RNA sequencing

Klotho knock-out mice are an important model for CKD-induced calcification. In CKD, serum magnesium (Mg2+) inversely correlates with vascular calcification. This study aims to determine the effects of Mg2+ on aortic calcification in Klotho knock-out mice. Klotho knock-out mice were treated with either a minimal or a high Mg2+ diet from birth. After eight weeks, serum biochemistry was studied and organs were harvested. Protective effects of Mg2+ were characterized by RNA-sequencing of aortic tissue. Micro-CT analysis was performed to study bone integrity. High Mg2+ diet prevented vascular calcification and reduced aortic gene expression of Runx2 and matrix Gla protein, demonstrating the protective effect on pro-osteogenic signaling. Differential expression of inflammation and extracellular matrix remodeling genes accompany the beneficial effects of Mg2+ on calcification. High dietary Mg2+ did not affect serum parathyroid hormone, vitamin D3 and calcium. High Mg2+ intake prevented calcification despite increasing fibroblast growth factor-23 and phosphate concentration in knock-out mice. In addition, mice on the high Mg2+ diet had a 20% reduced femoral bone mineral density and increased osteoid formation indicating osteomalacia, while osteoclast activity was decreased in Klotho knock-out mice. In Saos-2 osteoblasts, Mg2+ supplementation reduced mineralization independent of osteoblastic matrix production, alkaline phosphatase activity and maturation markers alpha-1 type-I collagen and sclerostin. In conclusion, high dietary Mg2+ prevents calcification in Klotho knock-out mice. These effects are potentially mediated by reduction of inflammatory and extracellular matrix remodeling pathways in the aorta. Mg2+ treatment is promising to prevent vascular calcification, but the risk for osteomalacia should be considered. SOURCE: Jeroen,H.F.,de Baaij (jeroen.debaaij@radboudumc.nl) - Ion Transport Radboudumc