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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Effect of calcium-based versus non-calcium-based phosphate binders on mortality in patients with chronic kidney disease: an updated systematic review and meta-analysis
Sophie A. Jamal,Sophie A. Jamal,Ben Vandermeer,Paolo Raggi,David C. Mendelssohn,David C. Mendelssohn,Trish Chatterley,Marlene Dorgan,Charmaine E. Lok,David Fitchett,Ross T. Tsuyuki +10 more
TL;DR: Analysis of the 11 randomised trials that reported an outcome of mortality showed that patients assigned to non-calcium-based binders had a 22% reduction in all-cause mortality compared with those assigned to calcium-based phosphate binders.
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Bioinorganics and biomaterials: bone repair.
TL;DR: It is illustrated that inorganics can positively affect bone healing but various factors make literature comparisons difficult and Bioinorganics have the potential to have just as big an impact on bone regeneration as recombinant proteins without some of the safety concerns and high costs.
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Hyperphosphatemia of chronic kidney disease
TL;DR: The characterization of hyperphosphatemia of chronic kidney disease as a distinct syndrome in clinical medicine with unique disordered skeletal remodeling, heterotopic mineralization and cardiovascular morbidity is presented.
Journal ArticleDOI
Bone Morphogenetic Proteins in Vascular Calcification
TL;DR: The role of BMP-2 in vascular calcification is not proven, but it has been the most studied member of the BMP family in this disease process, and it may be through inducing osteoblastic differentiation of VSMCs through induction of MSX-2, or by inducing apoptosis ofVSMCs, a process thought critical in the initiation ofascular calcification.
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Update on fibroblast growth factor 23 in chronic kidney disease
TL;DR: A critical review of the effects of different therapeutic strategies targeting FGF23 reduction and how these might be leveraged in a future randomized trial aimed at improving outcomes in CKD is concluded.
References
More filters
Journal ArticleDOI
Osf2/Cbfa1: A Transcriptional Activator of Osteoblast Differentiation
TL;DR: Cloned cDNA encoding Osf2/Cbfa1 is identified as an osteoblast-specific transcription factor and as a regulator of osteoblasts differentiation.
Journal ArticleDOI
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Makoto Kuro-o,Matsumura Yutaka,Hiroki Aizawa,Hiroshi Kawaguchi,Tatsuo Suga,Toshihiro Utsugi,Yoshio Ohyama,Masahiko Kurabayashi,Tadashi Kaname,Eisuke Kume,Hitoshi Iwasaki,Akihiro Iida,Takako Shiraki-Iida,Satoshi Nishikawa,Ryozo Nagai,Ryozo Nagai,Yo-ichi Nabeshima +16 more
TL;DR: A new gene, termed klotho, has been identified that is involved in the suppression of several ageing phenotypes in the mouse, and may function as part of a signalling pathway that regulates ageing in vivo and morbidity in age-related diseases.
Journal ArticleDOI
Cbfa1, a Candidate Gene for Cleidocranial Dysplasia Syndrome, Is Essential for Osteoblast Differentiation and Bone Development
Florian Otto,Anders P Thornell,Tessa Crompton,Angela Denzel,Kimberly C Gilmour,Ian R Rosewell,Gordon Stamp,Rosa S.P Beddington,Stefan Mundlos,Bjorn R. Olsen,Paul B. Selby,Michael John Owen +11 more
TL;DR: The Cbfa1 gene is essential for osteoblast differentiation and bone formation, and the C bfa1 heterozygous mouse is a paradigm for a human skeletal disorder.
Journal ArticleDOI
Coronary-Artery Calcification in Young Adults with End-Stage Renal Disease Who Are Undergoing Dialysis
William G. Goodman,Jonathan G. Goldin,Beatriz D. Kuizon,Chun Yoon,Barbara Gales,Donna Sider,Yan Wang,Joanie Chung,Aletha Emerick,Lloyd E. Greaser,Robert Elashoff,Isidro B. Salusky +11 more
TL;DR: Coronary-artery calcification is common and progressive in young adults with end-stage renal disease who are undergoing dialysis who are undergoing dialysis.
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Makoto Kuro-o,Matsumura Yutaka,H. Arawa,Hiroshi Kawaguchi,Tatsuo Suga,Toshihiro Utsugi,Yoshio Ohyama,Masahiko Kurabayashi,Tadashi Kaname,Eisuke Kume,H. Iwasaki,Akihiro Iida,Takako Shiraki-Iida,Satoshi Nishikawa,Ryozo Nagai,Yo-ichi Nabeshima,K. Sharma,L. Kelly,T. Dandekar +18 more
TL;DR: A new gene, termed klotho, has been identified that is involved in the suppression of several ageing phenotypes in the mouse, including short lifespan, infertility, arteriosclerosis, skin atrophy, osteoporosis and emphysema as mentioned in this paper.