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https://www.readbyqxmd.com/read/29344330/developments-in-rare-bone-diseases-and-mineral-disorders
#1
REVIEW
Siobhan Bacon, Rachel Crowley
In the last decade, there have been a number of significant advances made in the field of rare bone diseases. In this review, we discuss the expansion of the classification system for osteogenesis imperfecta (OI) and the resultant increase in therapeutic options available for management of OI. Bisphosphonates remain the most widely used intervention for OI, although the effect on fracture rate reduction is equivocal. We review the other therapies showing promising results, including denosumab, teriparatide, sclerostin, transforming growth factor β inhibition and gene targeted approaches...
January 2018: Therapeutic Advances in Chronic Disease
https://www.readbyqxmd.com/read/29342138/%C3%AE-klotho-is-a-non-enzymatic-molecular-scaffold-for-fgf23-hormone-signalling
#2
Gaozhi Chen, Yang Liu, Regina Goetz, Lili Fu, Seetharaman Jayaraman, Ming-Chang Hu, Orson W Moe, Guang Liang, Xiaokun Li, Moosa Mohammadi
The ageing suppressor α-klotho binds to the fibroblast growth factor receptor (FGFR). This commits FGFR to respond to FGF23, a key hormone in the regulation of mineral ion and vitamin D homeostasis. The role and mechanism of this co-receptor are unknown. Here we present the atomic structure of a 1:1:1 ternary complex that consists of the shed extracellular domain of α-klotho, the FGFR1c ligand-binding domain, and FGF23. In this complex, α-klotho simultaneously tethers FGFR1c by its D3 domain and FGF23 by its C-terminal tail, thus implementing FGF23-FGFR1c proximity and conferring stability...
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29342135/structures-of-%C3%AE-klotho-reveal-a-zip-code-like-mechanism-for-endocrine-fgf-signalling
#3
Sangwon Lee, Jungyuen Choi, Jyotidarsini Mohanty, Leiliane P Sousa, Francisco Tome, Els Pardon, Jan Steyaert, Mark A Lemmon, Irit Lax, Joseph Schlessinger
Canonical fibroblast growth factors (FGFs) activate FGF receptors (FGFRs) through paracrine or autocrine mechanisms in a process that requires cooperation with heparan sulfate proteoglycans, which function as co-receptors for FGFR activation. By contrast, endocrine FGFs (FGF19, FGF21 and FGF23) are circulating hormones that regulate critical metabolic processes in a variety of tissues. FGF19 regulates bile acid synthesis and lipogenesis, whereas FGF21 stimulates insulin sensitivity, energy expenditure and weight loss...
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29337188/abrogation-of-fam20c-altered-cell-behaviors-and-bmp-signaling-of-immortalized-dental-mesenchymal-cells
#4
Chao Liu, Nan Zhou, Yu Wang, Hua Zhang, Priyam Jani, Xiaofang Wang, Yongbo Lu, Nan Li, Jing Xiao, Chunlin Qin
FAM20C mutations compromise the mineralization of skeleton and tooth in both human and mouse. Putatively, the mineralization disorder is attributed to the elevated fibroblast growth factor 23 (FGF23), which reduced the serum phosphorus by suppressing the reabsorption of phosphorus in kidney. Besides the regulation on systemic phosphorus homeostasis, FAM20C was also implicated to regulate cell behaviors and gene expression through a cell-autonomous manner. To identify the primary effects of Fam20c on dental mesenchymal cells, mouse Fam20c-deficient dental mesenchymal cells were generated by removing the floxed alleles from the immortalized mouse Fam20cf/f dental mesenchymal cells with Cre-expressing lentivirus...
January 11, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29336609/fibroblast-growth-factor-23-fgf23-gene-polymorphisms-are-associated-with-essential-hypertension-risk-and-blood-pressure-levels-in-chinese-han-population
#5
Peng Cai, Yan Peng, Li Li, Wei Chu, Xukai Wang
In this case-control study, 246 EH patients and 157 healthy controls were selected from Chinese Han population to explore the associations between the fibroblast growth factor 23 (FGF23) gene polymorphisms and essential hypertension (EH).The SequenomMassarray system was used for the genotyping of three FGF23 gene Tag single-nucleotide polymorphisms, namely rs7955866, rs13312756, and rs3812822. The primers were designed by Assay Designer 3.1 software, and then the samples were added to a 384-well plate for the polymerase chain reaction amplification, shrimp alkaline phosphatase reaction, and desalting after extension...
January 16, 2018: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/29334610/phase-ii-study-of-dovitinib-in-patients-with-castration-resistant-prostate-cancer-kcsg-gu11-05
#6
Yoon Ji Choi, Hye Sook Kim, Se Hoon Park, Bong-Seog Kim, Kyoung Ha Kim, Hyo Jin Lee, Hong Suk Song, Dong-Yeop Shin, Ha Young Lee, Hoon-Gu Kim, Kyung Hee Lee, Jae Lyun Lee, Kyong Hwa Park
Purpose: Fibroblast growth factor (FGF) signals are important in carcinogenesis and progression of prostate cancer. Dovitinib is an oral, pan-class inhibitor of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, and fibroblast growth factor receptor (FGFR). We evaluated the efficacy and toxicity of dovitinib in men with metastatic castration resistant prostate cancer (mCRPC). Materials and Methods: This study was a single-arm, phase II, open-label, multicenter trial of dovitinib 500mg/day (5-days-on/2-days-off schedule)...
January 2, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29325128/relationship-between-twelve-adipocytokines-and-distinct-components-of-the-metabolic-syndrome
#7
Thomas Ebert, Claudia Gebhardt, Markus Scholz, Tobias Wohland, Dorit Schleinitz, Mathias Fasshauer, Matthias Blüher, Michael Stumvoll, Peter Kovacs, Anke Tönjes
Objective: Adipose tissue-derived signals potentially link obesity and adipose tissue dysfunction with metabolic and cardiovascular diseases. Although some adipocytokines have been closely related to metabolic and cardiovascular traits, it remains open which adipocytokine or adipocytokine cluster serve as meaningful marker of metabolic syndrome (MS) components. Therefore, this study investigates the associations of twelve adipocytokines with components of the MS to identify the most relevant cytokines potentially related to specific metabolic profiles...
January 9, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29309658/genetic-background-influences-cardiac-phenotype-in-murine-chronic-kidney-disease
#8
Samantha Neuburg, Corey Dussold, Claire Gerber, Xueyan Wang, Connor Francis, Lixin Qi, Valentin David, Myles Wolf, Aline Martin
Background: Levels of fibroblast growth factor 23 (FGF23) increase early in chronic kidney disease (CKD) and are independently associated with left ventricular hypertrophy (LVH), heart failure and death. Experimental models of CKD with elevated FGF23 and LVH are needed. We hypothesized that slow rates of CKD progression in the Col4a3 knockout (Col4a3KO) mouse model of CKD would promote development of LVH by prolonging exposure to elevated FGF23. Methods: We studied congenic Col4a3KO and wild-type (WT) mice with either 75% 129X1/SvJ (129Sv) or 94% C57Bl6/J (B6) genomes...
December 22, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29306478/fibroblast-growth-factor-23-is-related-to-profiles-indicating-volume-overload-poor-therapy-optimization-and-prognosis-in-patients-with-new-onset-and-worsening-heart-failure
#9
Jozine M Ter Maaten, Adriaan A Voors, Kevin Damman, Peter van der Meer, Stefan D Anker, John G Cleland, Kenneth Dickstein, Gerasimos Filippatos, Pim van der Harst, Hans L Hillege, Chim C Lang, Marco Metra, Gerjan Navis, Leong Ng, Wouter Ouwerkerk, Piotr Ponikowski, Nilesh J Samani, Dirk J van Veldhuisen, Faiez Zannad, Aeilko H Zwinderman, Martin H de Borst
BACKGROUND: Fibroblast growth factor (FGF) 23 is a hormone that increases urinary phosphate excretion and regulates renal sodium reabsorption and plasma volume. We studied the role of plasma FGF23 in therapy optimization and outcomes in patients with new-onset and worsening heart failure (HF). METHODS: We measured plasma C-terminal FGF23 levels at baseline in 2399 of the 2516 patients included in the BIOlogy Study to Tailored Treatment in Chronic HF (BIOSTAT-CHF) trial...
February 15, 2018: International Journal of Cardiology
https://www.readbyqxmd.com/read/29304245/circulating-adiponectin-modifies-the-fgf23-response-to-vitamin-d-receptor-activation-a-post-hoc-analysis-of-a-double-blind-randomized-clinical-trial
#10
Belinda Spoto, Patrizia Pizzini, Giovanni Tripepi, Francesca Mallamaci, Carmine Zoccali
Background: The fibroblast growth factor 23 (FGF23) response to phosphate load is suppressed in adiponectin gene null mice and substantially amplified in mice overexpressing the same gene and vitamin D receptor (VDR) activation markedly enhances FGF23 gene expression. Methods: We performed an analysis of the static (baseline adiponectin levels) and dynamic (fluctuations in adiponectin levels) interactions of serum adiponectin with the FGF23 response to paricalcitol and placebo in the setting of a double-blind, randomized clinical trial in chronic kidney disease (CKD) patients (NCT01680198)...
February 3, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29301137/associations-of-fibroblast-growth-factor-23-with-markers-of-inflammation-and-leukocyte-transmigration-in-chronic-kidney-disease
#11
Carin Wallquist, Ladan Mansouri, Mattias Norrbäck, Britta Hylander, Stefan H Jacobson, Tobias E Larsson, Joachim Lundahl
BACKGROUND: Patients with chronic kidney disease (CKD) show elevated levels of inflammatory markers and have an increased risk of infections as well as cardiovascular morbidity. Recent studies have implied effects of fibroblast growth factor 23 (FGF23) on inflammation in CKD. We analyzed potential correlations between levels of FGF23 with pro-inflammatory chemokines and markers of leukocyte transmigration in CKD patients. METHODS: One hundred three patients with CKD 2-5ND and 54 healthy controls, had biochemical markers in blood and urine analyzed according to routine protocol...
January 4, 2018: Nephron
https://www.readbyqxmd.com/read/29298794/severe-fgf23-based-hypophosphataemic-osteomalacia-due-to-ferric-carboxymaltose-administration
#12
Klara Klein, Shonda Asaad, Michael Econs, Janet E Rubin
Ferric carboxymaltose (FCM) is a novel iron formulation increasingly prescribed due to its effectiveness and fast infusion time. FCM administration can cause an asymptomatic hypophosphataemia secondary to fibroblast growth factor 23 (FGF23) dysregulation. In patients with chronic iron needs, however, a severe, long-lasting hypophosphataemia can lead to osteomalacia with associated bone pain. Lack of awareness of this complication results in delayed time to diagnosis and significant morbidity. We report a case of a patient with Crohn's disease and chronic iron-deficiency anaemia receiving multiple doses of FCM who developed severe hypophosphataemic osteomalacia with urinary phosphate loss and increased FGF23...
January 3, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29288982/c-terminal-and-intact-fgf23-in-critical-illness-and-their-associations-with-acute-kidney-injury-and-in-hospital-mortality
#13
Karolina Rygasiewicz, Tomasz Hryszko, Andrzej Siemiatkowski, Szymon Brzosko, Alicja Rydzewska-Rosolowska, Beata Naumnik
BACKGROUND: FGF23 proved its value in prognostication of cardiovascular events and mortality among renal patients and general population. Limited data exist whether FGF23 may have any use in prediction of negative outcomes among critically ill patients admitted to intensive care unit (ICU). METHODS: Single center cohort study performed among patients admitted to ICU. The primary exposure was FGF23 plasma concentration measured within 24 h of ICU admission. The primary outcome was incident Acute Kidney Injury (AKI) and in-hospital mortality during the ICU stay...
December 27, 2017: Cytokine
https://www.readbyqxmd.com/read/29280738/genetic-causes-of-rickets
#14
Sezer Acar, Korcan Demir, Yufei Shi
Rickets is a metabolic bone disease that develops as a result of inadequate mineralization of growing bone due to disruption of calcium, phosphorus and/or vitamin D metabolism. Nutritional rickets remains a significant child health problem in developing countries. In addition, several rare genetic causes of rickets have also been described, which can be divided into two groups. The first group consists of genetic disorders of vitamin D biosynthesis and action, such as vitamin D-dependent rickets type 1A (VDDR1A), vitamin D-dependent rickets type 1B (VDDR1B), vitamin D-dependent rickets type 2A (VDDR2A), and vitamin D-dependent rickets type 2B (VDDR2B)...
December 27, 2017: Journal of Clinical Research in Pediatric Endocrinology
https://www.readbyqxmd.com/read/29279421/-bone-derived-hormones-and-their-systemic-regulation
#15
Yuichi Takashi, Seiji Fukumoto, Toshio Matsumoto
Bone has several functions such as supporting our body, protecting internal organs and contributing to hematopoiesis. Recently, it has been revealed that bone also works as an endocrine tissue and systemically regulates functions of other organs. It has been reported that fibroblast growth factor 23(FGF23)regulates phosphate metabolism and osteocalcin affect glucose/energy metabolism. In addition, sclerostin, interleukin-11(IL-11)and lipocalin 2 have been also found to be bone-derived humoral factors. Further investigation concerning the network systems among multiple organs via bone-derived hormones may lead to the development of new drugs...
2018: Clinical Calcium
https://www.readbyqxmd.com/read/29250031/new-insights-into-the-mechanism-of-action-of-soluble-klotho
#16
REVIEW
George D Dalton, Jian Xie, Sung-Wan An, Chou-Long Huang
The klotho gene encodes a type I single-pass transmembrane protein that contains a large extracellular domain, a membrane spanning segment, and a short intracellular domain. Klotho protein exists in several forms including the full-length membrane form (mKl) and a soluble circulating form [soluble klotho (sKl)]. mKl complexes with fibroblast growth factor receptors to form coreceptors for FGF23, which allows it to participate in FGF23-mediated signal transduction and regulation of phosphate and calcium homeostasis...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29190002/dentoalveolar-abscesses-not-associated-with-caries-or-trauma-a-diagnostic-hallmark-of-hypophosphatemic-rickets-initially-misdiagnosed-as-hypochondroplasia
#17
Silvia Elena Yacarini Paredes, Raquel Assed Bezerra Segato, Leila Daher Moreira, Alcides Moreira, Kranya Victoria Díaz Serrano, Clarissa Teles Rodrigues, Luciana Yamamoto Almeida, Jorge Esquiche León
Hypophosphatemic rickets is a rare genetic disorder involving the regulation of fibroblast growth factor 23 (FGF23), a phosphaturic agent, clinically showing bowing of the legs, short stature and dentoalveolar abscesses. A 7-year-old boy, with previous hypochondroplasia diagnosis, was referred to our pediatric dentistry clinic presenting short stature, bone deformities and sinus tracts at deciduous teeth apex levels not related with trauma, restorations or dental caries. After deciduous teeth extraction, due to root resorption and mobility, light microscopy exhibited typical hypophosphatemic dentin, and micro-computed tomography revealed tubular clefts and porosities throughout the teeth...
November 30, 2017: Head and Neck Pathology
https://www.readbyqxmd.com/read/29181658/effect-of-ferric-citrate-hydrate-on-fgf23-and-pth-levels-in-patients-with-non-dialysis-dependent-chronic-kidney-disease-with-normophosphatemia-and-iron-deficiency
#18
Akira Iguchi, Suguru Yamamoto, Mihoko Yamazaki, Kazuyuki Tasaki, Yasushi Suzuki, Junichiro James Kazama, Ichiei Narita
BACKGROUND: In patients with normophosphatemia with chronic kidney disease (CKD), fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH) increase urinary phosphate excretion while maintaining serum phosphate within the normal range. Recent reports have shown that, in this stage, phosphate binders do not decrease serum FGF23 and PTH levels. Iron deficiency promotes transcription of FGF23 and iron-supplementation for iron deficiency decreases serum FGF23 levels. We hypothesized that ferric citrate hydrate, an iron-based phosphate binder, will decrease serum FGF23 levels in patients with non-dialysis-dependent CKD with normophosphatemia and iron deficiency...
November 27, 2017: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/29180266/heart-kidney-and-fgf23-les-liaisons-dangereuses
#19
EDITORIAL
Giuseppe Vergaro, Alberto Aimo, Claudio Passino, Michele Emdin
No abstract text is available yet for this article.
November 22, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/29179169/-bone-remodeling-through-a-phosphate-metabolism
#20
Takeshi Miyamoto
Phosphorus is the second abundant mineral stored in bones, and disturbance of phosphate metabolisms results in various disease developments such as hypophosphatemic rickets. Blood phosphorus levels are regulated by dietary intake or its absorption from intestine, proximal tubular reabsorption, and number of factors plays roles for maintaining phosphate homeostasis. Vitamin D stimulates intestinal phosphorus absorption, and phosphorus promotes FGF23 secretion from osteocytes. FGF23 inhibits Cyp27b1, an enzyme to produce an active vitamin D3, 1,25(OH)2D3, through FGF receptor/Klotho complex...
2017: Clinical Calcium
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