Phosphate regulation of vascular smooth muscle cell calcification.
Shuichi Jono,Marc D. McKee,Charles E. Murry,Atsushi Shioi,Yoshiki Nishizawa,Katsuhito Mori,Hirotoshi Morii,Cecilia M. Giachelli +7 more
TLDR
It is suggested that elevated phosphate may directly stimulate HSMCs to undergo phenotypic changes that predispose to calcification and offer a novel explanation of the phenomenon of vascular calcification under hyperphosphatemic conditions.Abstract:
Vascular calcification is a common finding in atherosclerosis and a serious problem in diabetic and uremic patients. Because of the correlation of hyperphosphatemia and vascular calcification, the ability of extracellular inorganic phosphate levels to regulate human aortic smooth muscle cell (HSMC) culture mineralization in vitro was examined. HSMCs cultured in media containing normal physiological levels of inorganic phosphate (1.4 mmol/L) did not mineralize. In contrast, HSMCs cultured in media containing phosphate levels comparable to those seen in hyperphosphatemic individuals (>1.4 mmol/L) showed dose-dependent increases in mineral deposition. Mechanistic studies revealed that elevated phosphate treatment of HSMCs also enhanced the expression of the osteoblastic differentiation markers osteocalcin and Cbfa-1. The effects of elevated phosphate on HSMCs were mediated by a sodium-dependent phosphate cotransporter (NPC), as indicated by the ability of the specific NPC inhibitor phosphonoformic acid, to dose dependently inhibit phosphate-induced calcium deposition as well as osteocalcin and Cbfa-1 gene expression. With the use of polymerase chain reaction and Northern blot analyses, the NPC in HSMCs was identified as Pit-1 (Glvr-1), a member of the novel type III NPCs. These data suggest that elevated phosphate may directly stimulate HSMCs to undergo phenotypic changes that predispose to calcification and offer a novel explanation of the phenomenon of vascular calcification under hyperphosphatemic conditions. The full text of this article is available at http://www.circresaha.org.read more
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Bioactive silica nanoparticles reverse age-associated bone loss in mice
M. Neale Weitzmann,M. Neale Weitzmann,Shin-Woo Ha,Tatyana Vikulina,Susanne Roser-Page,Susanne Roser-Page,Jin-Kyu Lee,George R. Beck,George R. Beck +8 more
TL;DR: The results showed that intra-peritoneal injections of silica nanoparticles could increase bone mineral density, with little observed toxic side effects, and suggest that osteogenic silicas nanoparticles may be a safe and effective therapeutic for counteracting age-associated bone loss.
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Phosphate-sensing and regulatory mechanism of FGF23 production
Y Takashi,S Fukumoto +1 more
TL;DR: It is proposed that FGFR1 works as a Pi-sensing receptor in the regulation of FGF23 production and serum Pi level, and this findings may lead to the development of new therapeutic methods to treat diseases caused by abnormal Pi level.
Journal ArticleDOI
FGF23/Klotho axis: phosphorus, mineral metabolism and beyond.
Javier Donate-Correa,Mercedes Muros-de-Fuentes,Carmen Mora-Fernández,Juan F. Navarro-González +3 more
TL;DR: The steps that allowed the identification of the fibroblast growth factor (FGF) 23/Klotho axis as the principal regulator of phosphate homeostasis, exerting actions on intestine, bone, parathyroid glands, and kidney are summarized.
Journal ArticleDOI
Pleiotropic effects of the non-calcium phosphate binder sevelamer.
I.G. Nikolov,I.G. Nikolov,N. Joki,Julien Maizel,Bernard Lacour,Tilman B. Drüeke,Ziad A. Massy +6 more
TL;DR: Sevelamer hydrochloride is a phosphate binder that offers an effective control of hyperphosphatemia as calcium-rich binders but without increase of calcium load.
Journal ArticleDOI
CT-Detected Growth of Coronary Artery Calcification in Asymptomatic Middle-Aged Subjects and Association With 15 Biomarkers.
Søren Zöga Diederichsen,Mette H. Grønhøj,Hans Mickley,Oke Gerke,Flemming Hald Steffensen,Jess Lambrechtsen,Niels Peter Rønnow Sand,Lars Melholt Rasmussen,Michael H. Olsen,Axel Cosmus Pyndt Diederichsen +9 more
TL;DR: Low-density lipoprotein and total cholesterol were associated with CAC incidence and phosphate with CAC progression, whereas 12 other biomarkers had little value.
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