The Experts below are selected from a list of 249 Experts worldwide ranked by ideXlab platform
Shawkat M Razzaque - One of the best experts on this subject based on the ideXlab platform.
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does fgf23 klotho activity influence vascular and Soft Tissue Calcification through regulating phosphate homeostasis
Kidney International, 2008Co-Authors: Fahad Memon, Mohga Elabbadi, Teruyo Nakatani, Takashi Taguchi, Beate Lanske, Shawkat M RazzaqueAbstract:Recent studies describe a novel role of fibroblast growth factor 23 (Fgf23)-klotho activity in the systemic regulation of calcium and phosphate homeostasis. Both Fgf23 and klotho ablated mice develop extensive vascular and Soft Tissue Calcification. Inability to clear the required amount of phosphate by the kidney, due to the absence of Fgf23-klotho activity, leads to increased serum accumulation of phosphate in these genetically modified mice, causing extensive Calcification. Serum calcium levels are also elevated in both Fgf23 and klotho ablated mice. Moreover, increased sodium-phosphate co-transporter activity in both Fgf23 and klotho ablated mice increases renal phosphate reabsorption which in turn can facilitate Calcification. Collectively, these observations bring new insights into our understanding of the roles of the Fgf23-klotho axis in the development of vascular and Soft Tissue Calcification.
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does fgf23 klotho activity influence vascular and Soft Tissue Calcification through regulating mineral ion metabolism
Kidney International, 2008Co-Authors: Fahad Memon, Mohga Elabbadi, Teruyo Nakatani, Takashi Taguchi, Beate Lanske, Shawkat M RazzaqueAbstract:Recent studies describe a novel role of fibroblast growth factor-23 (Fgf23)–klotho activity in the systemic regulation of calcium and phosphate homeostasis. Both Fgf23 and klotho ablated mice develop extensive vascular and Soft Tissue Calcification. Inability to clear the required amount of phosphate by the kidney, due to the absence of Fgf23–klotho activity, leads to increased accumulation of serum phosphate in these genetically modified mice, causing extensive Calcification. Serum calcium and 1,25 hydroxyvitamin D levels are also elevated in both Fgf23 and klotho ablated mice. Moreover, increased sodium phosphate co-transporter activity in both Fgf23 and klotho ablated mice increases renal phosphate reabsorption which in turn can facilitate Calcification. Collectively, these observations bring new insights into our understanding of the roles of the Fgf23–klotho axis in the development of vascular and Soft Tissue Calcification.
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does fgf23 ndash klotho activity influence vascular and Soft Tissue Calcification through regulating mineral ion metabolism
Kidney International, 2008Co-Authors: Fahad Memon, Mohga Elabbadi, Teruyo Nakatani, Takashi Taguchi, Beate Lanske, Shawkat M RazzaqueAbstract:Recent studies describe a novel role of fibroblast growth factor-23 (Fgf23)–klotho activity in the systemic regulation of calcium and phosphate homeostasis. Both Fgf23 and klotho ablated mice develop extensive vascular and Soft Tissue Calcification. Inability to clear the required amount of phosphate by the kidney, due to the absence of Fgf23–klotho activity, leads to increased accumulation of serum phosphate in these genetically modified mice, causing extensive Calcification. Serum calcium and 1,25 hydroxyvitamin D levels are also elevated in both Fgf23 and klotho ablated mice. Moreover, increased sodium phosphate co-transporter activity in both Fgf23 and klotho ablated mice increases renal phosphate reabsorption which in turn can facilitate Calcification. Collectively, these observations bring new insights into our understanding of the roles of the Fgf23–klotho axis in the development of vascular and Soft Tissue Calcification.
Benjamin Landing - One of the best experts on this subject based on the ideXlab platform.
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Soft Tissue Calcification in pediatric patients with end stage renal disease
Kidney International, 1990Co-Authors: Dawn S Milliner, Alan R Zinsmeister, Ellin Lieberman, Benjamin LandingAbstract:Soft Tissue Calcification in pediatric patients with end-stage renal disease. Soft Tissue Calcification is a recognized complication of uremia in adult patients and has been implicated as a cause of ischemic necrosis, cardiac arrhythmias, and respiratory failure. However, Soft Tissue Calcification has been regarded as rare in pediatric renal patients. Following a sudden death due to pulmonary calcinosis in an adolescent after renal transplantation, we retrospectively reviewed clinical, biochemical and autopsy data of 120 patients with uremia, on dialysis, or following renal transplantation cared for at Childrens Hospital of Los Angeles from 1960 to 1983. Soft Tissue Calcification was found in 72 of 120 patients (60 percent). Forty-three patients (36 percent) had systemic calcinosis (Group A); the most frequent sites of mineral deposition were blood vessels, lung, kidney, myocardium, coronary artery, central nervous system, and gastric mucosa. Vascular Calcification was uniformly accompanied by deposits in other organs. Twenty-nine patients had small amounts of focal Calcification (Group B) and 48 patients had no Soft Tissue Calcification (Group C). By multiple logistic regression analysis, the use of vitamin D or its analogues, the form of vitamin D medication prescribed, the peak calcium × phosphorus product, the age at onset of renal failure, and male sex were jointly associated with calcinosis (Group A). Vitamin D therapy showed the strongest independent association with calcinosis and the probability of calcinosis was greater in patients receiving calcitriol when compared with dihydrotachysterol and vitamin D 2 or D 3 . The duration of renal failure, peak serum calcium, serum calcium at death, serum phosphorus at death, and primary renal diagnosis, were not statistically associated with calcinosis. The data from this series confirm that Soft Tissue Calcification is a significant problem in young patients with advanced renal disease. Lung, myocardium, and coronary arteries were frequent sites of calcium deposition, with clinically significant, and in some cases fatal consequences.
Hongwei Ouyang - One of the best experts on this subject based on the ideXlab platform.
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pharmacological regulation of in situ Tissue stem cells differentiation for Soft Tissue Calcification treatment
Stem Cells, 2016Co-Authors: Jiajie Hu, Weiliang Shen, Ping Lu, Minjian Kong, Boon Chin Heng, Yi Ting Zhou, Weishan Chen, Xiao Chen, Hongwei OuyangAbstract:Calcification of Soft Tissues, such as heart valves and tendons, is a common clinical problem with limited therapeutics. Tissue specific stem/progenitor cells proliferate to repopulate injured Tissues. But some of them become divergent to the direction of ossification in the local pathological microenvironment, thereby representing a cellular target for pharmacological approach. We observed that HIF-2alpha (encoded by EPAS1 inclined form) signaling is markedly activated within stem/progenitor cells recruited at calcified sites of diseased human tendons and heart valves. Proinflammatory microenvironment, rather than hypoxia, is correlated with HIF-2alpha activation and promoted osteochondrogenic differentiation of tendon stem/progenitor cells (TSPCs). Abnormal upregulation of HIF-2alpha served as a key switch to direct TSPCs differentiation into osteochondral-lineage rather than teno-lineage. Notably, Scleraxis (Scx), an essential tendon specific transcription factor, was suppressed on constitutive activation of HIF-2alpha and mediated the effect of HIF-2alpha on TSPCs fate decision. Moreover, pharmacological inhibition of HIF-2alpha with digoxin, which is a widely utilized drug, can efficiently inhibit Calcification and enhance tenogenesis in vitro and in the Achilles's tendinopathy model. Taken together, these findings reveal the significant role of the Tissue stem/progenitor cells fate decision and suggest that pharmacological regulation of HIF-2alpha function is a promising approach for Soft Tissue Calcification treatment. Stem Cells 2016;34:1083–1096
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manipulating stem cells to treat Calcification pharmacological regulation of in situ Tissue stem cells differentiation for Soft Tissue Calcification treatment
Stem Cells, 2016Co-Authors: Jiajie Hu, Weiliang Shen, Ping Lu, Minjian Kong, Boon Chin Heng, Yi Ting Zhou, Weishan Chen, Xiao Chen, Hongwei OuyangAbstract:Abstract Calcification of Soft Tissues, such as heart valves and tendons, is a common clinical problem with limited therapeutics. Tissue specific stem/progenitor cells proliferate to repopulate injured Tissues. But some of them become divergent to the direction of ossification in the local pathological microenvironment, thereby representing a cellular target for pharmacological approach. We observed that HIF-2alpha (encoded by EPAS1) signaling is markedly activated within stem/progenitor cells recruited at calcified sites of diseased human tendons and heart valves. Proinflammatory microenvironment, rather than hypoxia, is correlated with HIF-2alpha activation and promoted osteochondrogenic differentiation of tendon stem/progenitor cells (TSPCs). Abnormal upregulation of HIF-2alpha served as a key switch to direct TSPCs differentiation into osteochondral-lineage rather than teno-lineage. Notably, Scleraxis (Scx), an essential tendon specific transcription factor, was suppressed upon constitutive activation of HIF-2alpha and mediated the effect of HIF-2alpha on TSPCs fate decision. Moreover, pharmacological inhibition of HIF-2alpha with digoxin, which is a widely utilized drug, can efficiently inhibit Calcification and enhance tenogenesis in vitro and in the Achilles's tendinopathy model. Taken together, these findings reveal the significant role of the Tissue stem/progenitor cells fate decision and suggest that pharmacological regulation of HIF-2alpha function is a promising approach for Soft Tissue Calcification treatment. This article is protected by copyright. All rights reserved.
Jijnasa Bordoloi - One of the best experts on this subject based on the ideXlab platform.
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implication of a novel vitamin k dependent protein grp ucma in the pathophysiological conditions associated with vascular and Soft Tissue Calcification osteoarthritis inflammation and carcinoma
International Journal of Biological Macromolecules, 2018Co-Authors: Jijnasa Bordoloi, Anjum Dihingia, Jatin Kalita, Prasenjit MannaAbstract:Abstract Gla-rich protein (GRP) or unique cartilage matrix-associated protein (Ucma), the newest member of vitamin K dependent proteins, carries exceptionally high number of γ-carboxyglutamic acid (Gla) residues which contributes to its outstanding capacity of binding with calcium in the extracellular environment indicating its potential role as a global calcium modulator. Recent studies demonstrated a critical function of GRP in the regulation of different pathophysiological conditions associated with vascular and Soft Tissue Calcification including cardiovascular diseases, osteoarthritis, inflammation, and skin and breast carcinomas. These findings established an important relationship between γ-carboxylation of GRP and Calcification associated disease pathology suggesting a critical role of vitamin K in the pathophysiological features of various health disorders. This review for the first time summarizes all of the updated findings related to the functional activities of GRP in the pathogenesis of several diseases associated with vascular and Soft Tissue mineralization, osteoarthritis, inflammation, and carcinoma. The outcome of this review will improve the understanding about the role of GRP in the pathogenesis of Tissue Calcification and its associated health disorders, which should in turn lead to the design of clinical interventions to improve the condition of patients associated with these health disorders.
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Implication of a novel vitamin K dependent protein, GRP/Ucma in the pathophysiological conditions associated with vascular and Soft Tissue Calcification, osteoarthritis, inflammation, and carcinoma.
International Journal of Biological Macromolecules, 2018Co-Authors: Jijnasa Bordoloi, Anjum Dihingia, Jatin Kalita, Prasenjit MannaAbstract:Abstract Gla-rich protein (GRP) or unique cartilage matrix-associated protein (Ucma), the newest member of vitamin K dependent proteins, carries exceptionally high number of γ-carboxyglutamic acid (Gla) residues which contributes to its outstanding capacity of binding with calcium in the extracellular environment indicating its potential role as a global calcium modulator. Recent studies demonstrated a critical function of GRP in the regulation of different pathophysiological conditions associated with vascular and Soft Tissue Calcification including cardiovascular diseases, osteoarthritis, inflammation, and skin and breast carcinomas. These findings established an important relationship between γ-carboxylation of GRP and Calcification associated disease pathology suggesting a critical role of vitamin K in the pathophysiological features of various health disorders. This review for the first time summarizes all of the updated findings related to the functional activities of GRP in the pathogenesis of several diseases associated with vascular and Soft Tissue mineralization, osteoarthritis, inflammation, and carcinoma. The outcome of this review will improve the understanding about the role of GRP in the pathogenesis of Tissue Calcification and its associated health disorders, which should in turn lead to the design of clinical interventions to improve the condition of patients associated with these health disorders.
Escolastico Aguileratejero - One of the best experts on this subject based on the ideXlab platform.
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metabolic acidosis inhibits Soft Tissue Calcification in uremic rats
Kidney International, 2008Co-Authors: F J Mendoza, Mariano Rodriguez, Ignacio Gonzalez Lopez, J. Pérez, Escolastico AguileratejeroAbstract:Metabolic acidosis is common in patients with chronic kidney disease, which is known to affect bone metabolism. We examined the effect of metabolic acidosis on the development of vascular and other Soft-Tissue Calcifications in uremic rats treated with calcitriol. Extraskeletal Calcification was measured in vivo, in control rats and rats with a remnant kidney model of uremia with or without ammonium chloride-induced acidosis. Soft-Tissue Calcification was assessed histologically, by measurement of the expression of the sodium-dependent phosphate cotransporter Pit-1 and by quantification of Tissue calcium and phosphorus. Calcitriol administration to uremic rats resulted in significant deposition of material positive for von Kossa stain in the aorta, stomach, and kidney, elevated aortic calcium and phosphorus, increased aortic Pit-1 expression, and high mortality. Calcitriol-treated uremic rats with acidosis did not develop aortic or Soft-Tissue Calcification, did not increase aortic Pit-1 expression, and had significantly lower mortality. Additionally, an acidotic environment prevented Calcification of vascular smooth muscle cells in vitro. Our study shows that metabolic acidosis inhibits extraskeletal Calcification.
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the effect of calcitriol paricalcitol and a calcimimetic on extraosseous Calcifications in uremic rats
Kidney International, 2008Co-Authors: Ignacio Gonzalez Lopez, F J Mendoza, Escolastico Aguileratejero, Fatima Guerrero, J. Pérez, David Martin, Mariano RodriguezAbstract:Vitamin D derivatives and calcimimetics are used to treat secondary hyperparathyroidism in patients with chronic renal failure. We investigated the effect of calcitriol, paricalcitol, and the calcimimetic AMG 641 on Soft-Tissue Calcification in uremic rats with secondary hyperparathyroidism. Control and uremic rats were treated with vehicle, calcitriol, paricalcitol, AMG 641, or a combination of AMG 641 plus calcitriol or paricalcitol. Parathyroid hormone levels were reduced by all treatments but were better controlled by the combination of paricalcitol and AMG 641. The calcimimetic alone did not induce extraosseous Calcification but co-administration of AMG 641 reduced Soft-Tissue Calcification and aortic mineralization in both calcitriol- and paricalcitol-treated rats. Survival was significantly reduced in rats treated with calcitriol and this mortality was attenuated by co-treatment with AMG 641. Our study shows that extraskeletal Calcification was present in animals treated with calcitriol and paricalcitol but not with AMG 641. When used in combination with paricalcitol, AMG 641 provided excellent control of secondary hyperparathyroidism and prevented mortality associated with the use of vitamin D derivatives without causing Tissue Calcification.
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metabolic acidosis inhibits Soft Tissue Calcification in uremic rats commentary
Kidney International, 2008Co-Authors: Z Alaly, F J Mendoza, Mariano Rodriguez, Ignacio Gonzalez Lopez, J. Pérez, Escolastico AguileratejeroAbstract:Metabolic acidosis is common in patients with chronic kidney disease, which is known to affect bone metabolism. We examined the effect of metabolic acidosis on the development of vascular and other Soft-Tissue Calcifications in uremic rats treated with calcitriol. Extraskeletal Calcification was measured in vivo, in control rats and rats with a remnant kidney model of uremia with or without ammonium chloride-induced acidosis. Soft-Tissue Calcification was assessed histologically, by measurement of the expression of the sodium-dependent phosphate cotransporter Pit-1 and by quantification of Tissue calcium and phosphorus. Calcitriol administration to uremic rats resulted in significant deposition of material positive for von Kossa stain in the aorta, stomach, and kidney, elevated aortic calcium and phosphorus, increased aortic Pit-1 expression, and high mortality. Calcitriol-treated uremic rats with acidosis did not develop aortic or Soft-Tissue Calcification, did not increase aortic Pit-1 expression, and had significantly lower mortality. Additionally, an acidotic environment prevented Calcification of vascular smooth muscle cells in vitro. Our study shows that metabolic acidosis inhibits extraskeletal Calcification.