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fibroblast growth factor 23

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https://www.readbyqxmd.com/read/28620244/specific-ablation-of-mouse-fam20c-in-cells-expressing-type-i-collagen-leads-to-skeletal-defects-and-hypophosphatemia
#1
Peihong Liu, Su Ma, Hua Zhang, Chao Liu, Yongbo Lu, Li Chen, Chunlin Qin
FAM20C mutations in humans cause Raine syndrome and our previous studies showed that global inactivation of mouse Fam20C led to bone and dental defects. By crossbreeding 2.3  kb Col 1a1-Cre mice with Fam20C (flox/flox) mice, we created 2.3  kb Col 1a1-Cre;Fam20C (foxl/flox) (cKO) mice, in which Fam20C was inactivated in cells expressing Type I collagen. This study showed that the long bones of cKO mice were shorter and had a lower level of mineralization compared to the normal mice. The collagen fibrils in Fam20C-deficient bone were disorganized and thicker while the growth plate cartilage in cKO mice was disorganized and wider compared to the normal mice...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28619026/elevated-serum-fibroblast-growth-factor-23-levels-as-an-indicator-of-lower-extremity-atherosclerotic-disease-in-chinese-patients-with-type-2-diabetes-mellitus
#2
Xingxing He, Xiang Hu, Xiaojing Ma, Hang Su, Lingwen Ying, Jiahui Peng, Xiaoping Pan, Yuqian Bao, Jian Zhou, Weiping Jia
BACKGROUND: Recently, basic and clinical studies have provided evidence supporting the relationship between circulating levels of fibroblast growth factor (FGF) 23 and the development of atherosclerosis. Given that diabetes is an established risk factor for lower extremity atherosclerotic disease (LEAD), the goal of the present study was to explore the relationship between serum FGF23 levels and LEAD, as well as the related factors, in Chinese patients with type 2 diabetes mellitus (T2DM)...
June 15, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28616218/soluble-klotho-may-be-a-marker-of-phosphate-reabsorption
#3
Sven-Jean Tan, Edward R Smith, Stephen G Holt, Tim D Hewitson, Nigel D Toussaint
Background: Membrane-bound α-klotho functions as a co-receptor with fibroblast growth factor receptor at the renal tubule conferring specificity to fibroblast growth factor-23 (FGF-23), allowing it to inhibit tubular phosphate reabsorption at physiological concentrations. α-klotho also exists as a soluble protein. However, the complex interrelationships between soluble α-klotho (sKl), FGF-23 and phosphate reabsorption are poorly understood, with little known about the links between sKl, FGF-23 and phosphate reabsorption in chronic kidney disease (CKD)...
June 2017: Clinical Kidney Journal
https://www.readbyqxmd.com/read/28615947/treatment-of-secondary-hyperparathyroidism-the-clinical-utility-of-etelcalcetide
#4
REVIEW
Mario Cozzolino, Andrea Galassi, Ferruccio Conte, Michela Mangano, Luca Di Lullo, Antonio Bellasi
Secondary hyperparathyroidism (SHPT), a very frequent, severe, and worsening complication of chronic kidney disease, is characterized by high serum parathyroid hormone (PTH), parathyroid gland hyperplasia, and disturbances in mineral metabolism. Clinically, SHPT shows renal osteodystrophy, vascular calcification, cardiovascular damage, and fatal outcome. Calcium-sensing receptor (CaSR) is the main physiological regulator of PTH secretion; its activation by calcium rapidly inhibits PTH. Another important player in regulating mineral metabolism is vitamin D receptor (VDR), which is under the influence of vitamin D and influences the intestinal absorption of calcium and phosphate, PTH gene expression, and bone calcium mobilization...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28614116/parathyroid-hormone-and-the-regulation-of-renal-tubular-calcium-transport
#5
Benjamin Ko
PURPOSE OF REVIEW: Renal tubule excretion of calcium is carefully and complexly regulated. At the center of this process, parathyroid hormone (PTH) is the chief regulator of renal calcium reabsorption. This review outlines our current understanding of PTH's effects on renal tubular calcium transport, focusing on the more recent discoveries beyond its direct regulation of epithelial Ca channel transient receptor potential vanilloid 5 (TRPV5) and looking at its interaction with sodium transport and the hormones fibroblast growth factor 23 (FGF23) and klotho...
June 12, 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28611350/fgf23-is-synthesised-locally-by-renal-tubules-and-activates-injury-primed-fibroblasts
#6
Edward R Smith, Sven-Jean Tan, Stephen G Holt, Tim D Hewitson
In kidney disease, higher circulating levels of the mineral-regulating hormone fibroblast growth factor (FGF)-23 are predictive of disease progression but direct pathogenic effects on the kidney are unknown. We sought evidence of local renal synthesis in response to unilateral ureteric obstruction in the mouse, and pro-fibrotic actions of FGF23 on the fibroblast in vitro. Acute tubulointerstitial injury due to unilateral ureteric obstruction stimulated renal FGF23 synthesis by tubules, and downregulated inactivating proprotein convertases, without effects on systemic mineral metabolism...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28600887/therapeutic-effects-of-fgf23-c-tail-fc-in-a-murine-pre-clinical-model-of-x-linked-hypophosphatemia-via-the-selective-modulation-of-phosphate-reabsorption
#7
Kristen Johnson, Kymberly Levine, Joseph Sergi, Jean Chamoun, Rachel Roach, Jackie Vekich, Mike Favis, Mark Horn, Xianjun Cao, Brian Miller, William Snyder, Dikran Aivazian, William Reagan, Edwin Berryman, Jennifer Colangelo, Victoria Markiewicz, Cedo Bagi, Thomas P Brown, Anthony Coyle, Moosa Mohammadi, Jeanne Magram
Fibroblast growth factor 23 (FGF23) is the causative factor of X-linked hypophosphatemia (XLH), a genetic disorder effecting 1:20,000 that is characterized by excessive phosphate excretion, elevated FGF23 levels and a rickets/osteomalacia phenotype. FGF23 inhibits phosphate reabsorption and suppresses 1α,25-dihydroxyvitamin D (1,25D) biosynthesis, analytes that differentially contribute to bone integrity and deleterious soft tissue mineralization. As inhibition of ligand broadly modulates downstream targets, balancing efficacy and unwanted toxicity is difficult when targeting the FGF23 pathway...
June 10, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28600880/klotho-lacks-a-fgf23-independent-role-in-mineral-homeostasis
#8
Olena Andrukhova, Jessica Bayer, Christiane Schüler, Ute Zeitz, Sathish K Murali, Sibel Ada, Jose M Alvarez-Pez, Alina Smorodchenko, Reinhold G Erben
Fibroblast growth factor-23 (FGF23) is a bone-derived hormone regulating vitamin D hormone production and renal handling of minerals by signaling through a FGF receptor/αKlotho (Klotho) receptor complex. Whether Klotho has FGF23-independent effects on mineral homeostasis is a controversial issue. Here, we aimed to shed more light on this controversy by comparing male and female triple knockout mice with simultaneous deficiency in Fgf23 and Klotho and a nonfunctioning vitamin D receptor (VDR) (Fgf23/Klotho/VDR) with double (Fgf23/VDR, Klotho/VDR, and Fgf23/Klotho) and single Fgf23, Klotho and VDR mutants...
June 10, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28596573/fibroblast-growth-factor-23-weakens-chemotaxis-of-human-blood-neutrophils-in-microfluidic-devices
#9
Ke Yang, Hagit Peretz-Soroka, Jiandong Wu, Ling Zhu, Xueling Cui, Michael Zhang, Claudio Rigatto, Yong Liu, Francis Lin
Neutrophil trafficking in tissues critically regulates the body's immune response. Neutrophil migration can either play a protective role in host defense or cause health problems. Fibroblast growth factor 23 (FGF23) is a known biomarker for chronic kidney disease (CKD) and was recently shown to impair neutrophil arrest on endothelium and transendothelial migration. In the present study, we further examined the effect of FGF23 on human blood neutrophil chemotaxis using two new microfluidic devices. Our results showed that chemotaxis of FGF23 pre-treated neutrophils to a fMLP gradient, in the presence or absence of a uniform FGF23 background, is quantitatively lower compared to the control cells...
June 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28595487/circulating-levels-of-vascular-endothelial-growth-factor-and-basic-fibroblastic-growth-factor-in-infantile-hemangioma-versus-vascular-malformations
#10
Nehal M El-Raggal, Rania A El-Farrash, Abeer A Saad, Enas A S Attia, Hatem A Saafan, Ibrahim S Shaaban
Few preliminary reports studied the utility of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) for differentiation between infantile hemangiomas (IHs) and vascular malformations. The aim of this study was to investigate the role of serum VEGF and bFGF levels in differentiating IHs from vascular malformations and identifying the stage and clinical course of IHs. Serum levels of VEGF and bFGF were assessed in 60 infants and children with various cutaneous vascular anomalies defined in 3 groups: proliferating IHs (n = 25), involuting IHs (n = 23), and vascular malformations (n = 12), in comparison with their levels in 40 healthy matched control...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/28594289/hypoxic-3d-cellular-network-construction-replicates-ex-vivo-the-phenotype-of-primary-human-osteocytes
#11
Saba Choudhary, Qiaoling Sun, Ciaran Mannion, Yair Kissin, Jenny Zilberberg, Woo Young Lee
Osteocytes are deeply embedded in the mineralized matrix of bone and are non-proliferative, making them a challenge to isolate and maintain using traditional in vitro culture methods without sacrificing their inimitable phenotype. We studied the synergistic effects of two microenvironmental factors that are vital in retaining, ex vivo, the phenotype of primary human osteocytes: hypoxia and 3D cellular network. In order to recapitulate the lacunocanalicular structure of bone tissue, we assembled and cultured primary human osteocytic cells with biphasic calcium phosphate microbeads in a microfluidic perfusion culture device...
June 8, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28585053/circulating-levels-of-dickkopf-1-osteoprotegerin-and-sclerostin-are-higher-in-old-compared-with-young-men-and-women-and-positively-associated-with-whole-body-bone-mineral-density-in-older-adults
#12
J Coulson, L Bagley, Y Barnouin, S Bradburn, G Butler-Browne, H Gapeyeva, J-Y Hogrel, T Maden-Wilkinson, A B Maier, C Meskers, C Murgatroyd, M Narici, M Pääsuke, L Sassano, S Sipilä, N Al-Shanti, L Stenroth, D A Jones, J S McPhee
Bone mineral density declines with increasing older age. We examined the levels of circulating factors known to regulate bone metabolism in healthy young and older adults. The circulating levels of dickkopf-1, osteocalcin, osteoprotegerin and sclerostin were positively associated with whole-body bone mineral density (WBMD) in older adults, despite the average WBMD being lower and circulating dickkopf-1, osteoprotegerin and sclerostin being higher in old than young. INTRODUCTION: This study aims to investigate the relationship between whole-body bone mineral density (WBMD) and levels of circulating factors with known roles in bone remodelling during 'healthy' ageing...
June 5, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/28579423/serum-phosphorus-and-risk-of-cardiovascular-disease-all-cause-mortality-or-graft-failure-in-kidney-transplant-recipients-an-ancillary-study-of-the-favorit-trial-cohort
#13
Basma Merhi, Theresa Shireman, Myra A Carpenter, John W Kusek, Paul Jacques, Marc Pfeffer, Madhumathi Rao, Meredith C Foster, S Joseph Kim, Todd E Pesavento, Stephen R Smith, Clifton E Kew, Andrew A House, Reginald Gohh, Daniel E Weiner, Andrew S Levey, Joachim H Ix, Andrew Bostom
BACKGROUND: Mild hyperphosphatemia is a putative risk factor for cardiovascular disease [CVD], loss of kidney function, and mortality. Very limited data are available from sizable multicenter kidney transplant recipient (KTR) cohorts assessing the potential relationships between serum phosphorus levels and the development of CVD outcomes, transplant failure, or all-cause mortality. STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: The Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial, a large, multicenter, multiethnic, controlled clinical trial that provided definitive evidence that high-dose vitamin B-based lowering of plasma homocysteine levels did not reduce CVD events, transplant failure, or total mortality in stable KTRs...
June 2, 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/28577750/-strategies-aiming-to-control-hyperphosphatemia-in-chronic-kidney-disease
#14
Pablo Antonio Ureña Torres
Chronic kidney disease is known to be associated with phosphate retention. The mechanisms are complex and the early increase in serum phosphate levels in chronic kidney disease is not strictly related to the dietary phosphate load or to the degree of phosphate retention. It also implicates the activity of intestinal sodium-phosphate cotransporters, the degree of bone turnover and the retention and/or phosphate release from the skeleton, and the feedback mechanisms regulating the phosphaturia. Indeed, the increase in serum phosphate levels is only a reflection of underlying complex mechanisms, and many important factors play a role including parathyroid hormone, vitamin D, fibroblast growth factor 23 (FGF23), and others...
April 2017: Néphrologie & Thérapeutique
https://www.readbyqxmd.com/read/28571152/oncogenic-osteomalacia-an-approach-to-diagnosis-with-a-case-report
#15
Biswajit Dey, Debasis Gochhait, Hema Subramanian, Madhusudhanan Ponnusamy
Oncogenic osteomalacia, also known as tumour induced osteomalacia, is a rare paraneoplastic syndrome caused by mesenchymal tumours secreting Fibroblast Growth Factor-23 (FGF-23). The characteristic biochemical findings include hypophosphatemia and low 1,25-dihydroxy vitamin D. The differential diagnosis for hypophosphatemia are varied. We present a case of oncogenic osteomalacia in a 29-year-old female, who presented with complaints of generalized diffuse bone pain and walking difficulty for six months duration...
April 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28570697/correction-high-fibroblast-growth-factor-23-levels-are-associated-with-decreased-ferritin-levels-and-increased-intravenous-iron-doses-in-hemodialysis-patients
#16
(no author information available yet)
[This corrects the article DOI: 10.1371/journal.pone.0176984.].
2017: PloS One
https://www.readbyqxmd.com/read/28558021/interactions-of-sclerostin-with-fgf23-soluble-klotho-and-vitamin-d-in-renal-transplantation
#17
Lida Tartaglione, Marzia Pasquali, Silverio Rotondi, Maria Luisa Muci, Cristiana Leonangeli, Alessio Farcomeni, Valeria Fassino, Sandro Mazzaferro
Relationships of Sclerostin, a bone anti-anabolic protein, with biomarkers of mineral bone disorders in chronic kidney disease are still unsettled, in particular in kidney transplant (KTR). In 80 KTR patients (31F/49M, 54.7±10.3 years) we studied the relationships of serum Sclerostin with eGFR, Calcium, Phosphate, Alkaline Phosphatase (AP), intact Parathyroid hormone (iPTH), soluble alpha-Klotho (sKlotho), intact Fibroblast Growth Factor 23 (iFGF23), 25-hydroxyvitamin D(25D) and 1,25-dihydroxyvitamin D (1,25D)...
2017: PloS One
https://www.readbyqxmd.com/read/28554171/clearance-of-sclerostin-osteocalcin-fibroblast-growth-factor-23-and-osteoprotegerin-by-dialysis
#18
Nicholas Carlson, Ole H Mortensen, Mette Axelsen, Robert S Pedersen, James G Heaf
INTRODUCTION: Fibroblast growth factor (FGF23), sclerostin, osteocalcin, and osteoprotegerin are important factors that control mineral bone metabolism. End-stage renal disease is associated with the pronounced dysregulation of mineral bone metabolism; however, the impact and clearance of mineral bone metabolism factors during dialysis remain largely undescribed. METHODS: In a cross-sectional study, 10 chronic hemodialysis patients were treated with hemodialysis for 8 h using a high-flux filter and a dialysate bath of 50% calculated total body water continuously recycled at a rate of 500 mL/min...
2017: Blood Purification
https://www.readbyqxmd.com/read/28550081/randomized-controlled-trial-for-the-effect-of-vitamin-d-supplementation-on-vascular-stiffness-in-ckd
#19
Adeera Levin, Mila Tang, Taylor Perry, Nadia Zalunardo, Monica Beaulieu, Joshua A Dubland, Kelly Zerr, Ognjenka Djurdjev
BACKGROUND AND OBJECTIVES: Vitamin D is implicated in vascular health in CKD. This study compared placebo, calcifediol, and calcitriol treatment with changes in vascular stiffness, BP, proteinuria, mineral metabolism parameters, C-reactive protein, and fibroblast growth factor 23 in patients with stable CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a double-blind, randomized controlled trial in outpatient CKD clinics in Vancouver, Canada, from February of 2011 to August of 2014, enrolling 119 patients with an eGFR of 15-45 ml/min per 1...
May 26, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28540270/fgf-23-klotho-and-vitamin-d-levels-in-scleroderma
#20
Ravan Ahmadi, Mehrzad Hajialilo, Amir Ghorbanihaghjo, Ali Mota, Sina Raeisi, Nasrin Bargahi, Mohammad Valilo, Farahnaz Askarian
BACKGROUND: Scleroderma is a chronic connective tissue disease of unknown etiology. Vitamin D and parathyroid hormone (PTH) that play particular functions in calcium and phosphate homeostasis may be involved in the etiology of this disorder. Klotho, the co-receptor of the fibroblast growth factor 23 (FGF-23), can interfere with calcium and phosphate metabolism. The purpose of this study was to evaluate serum Klotho, FGF-23, intact PTH (iPTH) and vitamin D levels in scleroderma patients compared with the healthy controls...
April 2017: Iranian Journal of Public Health
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