Magnesium inhibits Wnt/β-catenin activity and reverses the osteogenic transformation of vascular smooth muscle cells.
Addy Montes de Oca,Fatima Guerrero,Julio M. Martinez-Moreno,Juan Antonio Madueño,Carmen Herencia,Alan Peralta,Yolanda Almaden,Ignacio González López,Escolastico Aguilera-Tejero,Kristina Gundlach,Janine Büchel,Mirjam E. Peter,Jutta Passlick-Deetjen,Mariano Rodriguez,Juan R. Muñoz-Castañeda +14 more
TLDR
In conclusion, magnesium transport through the cell membrane is important to inhibit VSMC calcification in vitro and inhibition of Wnt/β-catenin by magnesium is one potential intracellular mechanism by which this anti-calcifying effect is achieved.Abstract:
Magnesium reduces vascular smooth muscle cell (VSMC) calcification in vitro but the mechanism has not been revealed so far. This work used only slightly increased magnesium levels and aimed at determining: a) whether inhibition of magnesium transport into the cell influences VSMC calcification, b) whether Wnt/β-catenin signaling, a key mediator of osteogenic differentiation, is modified by magnesium and c) whether magnesium can influence already established vascular calcification. Human VSMC incubated with high phosphate (3.3 mM) and moderately elevated magnesium (1.4 mM) significantly reduced VSMC calcification and expression of the osteogenic transcription factors Cbfa-1 and osterix, and up-regulated expression of the natural calcification inhibitors matrix Gla protein (MGP) and osteoprotegerin (OPG). The protective effects of magnesium on calcification and expression of osteogenic markers were no longer observed in VSMC cultured with an inhibitor of cellular magnesium transport (2-aminoethoxy-diphenylborate [2-APB]). High phosphate induced activation of Wnt/β-catenin pathway as demonstrated by the translocation of β-catenin into the nucleus, increased expression of the frizzled-3 gene, and downregulation of Dkk-1 gene, a specific antagonist of the Wnt/β-catenin signaling pathway. The addition of magnesium however inhibited phosphate-induced activation of Wnt/β-catenin signaling pathway. Furthermore, TRPM7 silencing using siRNA resulted in activation of Wnt/β-catenin signaling pathway. Additional experiments were performed to test the ability of magnesium to halt the progression of already established VSMC calcification in vitro. The delayed addition of magnesium decreased calcium content, down-regulated Cbfa-1 and osterix and up-regulated MGP and OPG, when compared with a control group. This effect was not observed when 2-APB was added. In conclusion, magnesium transport through the cell membrane is important to inhibit VSMC calcification in vitro. Inhibition of Wnt/β-catenin by magnesium is one potential intracellular mechanism by which this anti-calcifying effect is achieved.read more
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Vascular Calcification-New Insights Into Its Mechanism.
TL;DR: To facilitate the understanding of vascular calcification, across any number of bioscientific disciplines, this review of a detailed updated molecular mechanism of VC encompasses a vascular smooth muscle phenotypic of osteogenic differentiation, and multiple signaling pathways of VC induction, including the roles of inflammation and cellular microorganelle genesis.
Journal ArticleDOI
WNT/β-catenin signaling promotes VSMCs to osteogenic transdifferentiation and calcification through directly modulating Runx2 gene expression.
TL;DR: It is suggested that high-phosphate may activate WNT/β-catenin signaling through different pathways, and the activated WNT-3A/ β-catanin signaling, through direct downstream target Runx2, could play an important role in promoting VOT and AMC.
Journal ArticleDOI
Signaling pathways involved in vascular smooth muscle cell calcification during hyperphosphatemia.
Jakob Voelkl,Florian Lang,Kai-Uwe Eckardt,Kerstin Amann,Makoto Kuro-o,Andreas Pasch,Burkert Pieske,Ioana Alesutan +7 more
TL;DR: Critical intracellular pathways controlling osteo-/chondrogenic transdifferentiation of VSMCs are addressed and elucidating these pathways holds a significant promise to open novel therapeutic opportunities counteracting the progression of vascular calcification in CKD.
Journal ArticleDOI
Dietary magnesium supplementation prevents and reverses vascular and soft tissue calcifications in uremic rats
Juan M. Díaz-Tocados,Alan Peralta-Ramírez,Alan Peralta-Ramírez,María E. Rodríguez-Ortiz,Ana I. Raya,Ignacio González López,Carmen Pineda,Carmen Herencia,Addy Montes de Oca,Noemi Vergara,Sonja Steppan,M. Victoria Pendón-Ruiz de Mier,Paula Buendía,Andrés Carmona,Julia Carracedo,Juan F. Alcala-Diaz,João M. Frazão,Julio M. Martinez-Moreno,Antonio Canalejo,Arnold J. Felsenfeld,Mariano Rodriguez,Escolastico Aguilera-Tejero,Yolanda Almaden,Juan R. Muñoz-Castañeda +23 more
TL;DR: Results of this study suggested that the protective effect of magnesium on vascular calcification was not limited to its action as an intestinal phosphate binder since magnesium administered intraperitoneally also decreased vascular calcifying.
Journal ArticleDOI
A Randomized Trial of Magnesium Oxide and Oral Carbon Adsorbent for Coronary Artery Calcification in Predialysis CKD.
Yusuke Sakaguchi,Takayuki Hamano,Yoshitsugu Obi,Chikako Monden,Tatsufumi Oka,Satoshi Yamaguchi,Isao Matsui,Nobuhiro Hashimoto,Ayumi Matsumoto,Karin Shimada,Yoshitsugu Takabatake,Atsushi Takahashi,Jun-ya Kaimori,Toshiki Moriyama,Ryohei Yamamoto,Masaru Horio,Koichi Yamamoto,Ken Sugimoto,Hiromi Rakugi,Yoshitaka Isaka +19 more
TL;DR: MgO, but not AST-120, appears to be effective in slowing CAC progression in CKD, and larger-scale trials are warranted to confirm these findings.
References
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