Effects of dietary phosphate on adynamic bone disease in rats with chronic kidney disease--role of sclerostin?

High phosphate intake is known to aggravate renal osteodystrophy along various pathogenetic pathways. Recent studies have raised the possibility that dysregulation of the osteocyte Wnt/β-catenin signaling pathway is also involved in chronic kidney disease (CKD)-related bone disease. We investigated...

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Autores principales:	Juliana C Ferreira, Guaraciaba O Ferrari, Katia R Neves, Raquel T Cavallari, Wagner V Dominguez, Luciene M Dos Reis, Fabiana G Graciolli, Elizabeth C Oliveira, Shiguang Liu, Yves Sabbagh, Vanda Jorgetti, Susan Schiavi, Rosa M A Moysés
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/781980599bad4e779c03aaa75fd55bd1
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spelling	oai:doaj.org-article:781980599bad4e779c03aaa75fd55bd12021-11-18T08:46:44ZEffects of dietary phosphate on adynamic bone disease in rats with chronic kidney disease--role of sclerostin?1932-620310.1371/journal.pone.0079721https://doaj.org/article/781980599bad4e779c03aaa75fd55bd12013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24236156/?tool=EBIhttps://doaj.org/toc/1932-6203High phosphate intake is known to aggravate renal osteodystrophy along various pathogenetic pathways. Recent studies have raised the possibility that dysregulation of the osteocyte Wnt/β-catenin signaling pathway is also involved in chronic kidney disease (CKD)-related bone disease. We investigated the role of dietary phosphate and its possible interaction with this pathway in an experimental model of adynamic bone disease (ABD) in association with CKD and hypoparathyroidism. Partial nephrectomy (Nx) and total parathyroidectomy (PTx) were performed in male Wistar rats. Control rats with normal kidney and parathyroid function underwent sham operations. Rats were divided into three groups and underwent pair-feeding for 8 weeks with diets containing either 0.6% or 1.2% phosphate: sham 0.6%, Nx+PTx 0.6%, and Nx+PTx 1.2%. In the two Nx+PTx groups, serum creatinine increased and blood ionized calcium decreased compared with sham control group. They also presented hyperphosphatemia and reduced serum parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) levels. Fractional urinary excretion of phosphate increased in Nx+PTx 1.2% rats despite lower PTH and FGF23 levels than in sham group. These biochemical changes were accompanied by a decrease in bone formation rates. The Nx+PTx 1.2% group had lower bone volume (BV/TV), higher osteoblast and osteocyte apoptosis, and higher SOST and Dickkopf-1 gene expression than the Nx+PTx 0.6% group. Nx+PTx 0.6% rat had very low serum sclerostin levels, and Nx+PTx 1.2% had intermediate sclerostin levels compared with sham group. Finally, there was a negative correlation between BV/TV and serum sclerostin. These results suggest that high dietary phosphate intake decreases bone volume in an experimental model of CKD-ABD, possibly via changes in SOST expression through a PTH-independent mechanism. These findings could have relevance for the clinical setting of CKD-ABD in patients who low turnover bone disease might be attenuated by optimal control of phosphate intake and/or absorption.Juliana C FerreiraGuaraciaba O FerrariKatia R NevesRaquel T CavallariWagner V DominguezLuciene M Dos ReisFabiana G GraciolliElizabeth C OliveiraShiguang LiuYves SabbaghVanda JorgettiSusan SchiaviRosa M A MoysésPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e79721 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Juliana C Ferreira Guaraciaba O Ferrari Katia R Neves Raquel T Cavallari Wagner V Dominguez Luciene M Dos Reis Fabiana G Graciolli Elizabeth C Oliveira Shiguang Liu Yves Sabbagh Vanda Jorgetti Susan Schiavi Rosa M A Moysés Effects of dietary phosphate on adynamic bone disease in rats with chronic kidney disease--role of sclerostin?
description	High phosphate intake is known to aggravate renal osteodystrophy along various pathogenetic pathways. Recent studies have raised the possibility that dysregulation of the osteocyte Wnt/β-catenin signaling pathway is also involved in chronic kidney disease (CKD)-related bone disease. We investigated the role of dietary phosphate and its possible interaction with this pathway in an experimental model of adynamic bone disease (ABD) in association with CKD and hypoparathyroidism. Partial nephrectomy (Nx) and total parathyroidectomy (PTx) were performed in male Wistar rats. Control rats with normal kidney and parathyroid function underwent sham operations. Rats were divided into three groups and underwent pair-feeding for 8 weeks with diets containing either 0.6% or 1.2% phosphate: sham 0.6%, Nx+PTx 0.6%, and Nx+PTx 1.2%. In the two Nx+PTx groups, serum creatinine increased and blood ionized calcium decreased compared with sham control group. They also presented hyperphosphatemia and reduced serum parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) levels. Fractional urinary excretion of phosphate increased in Nx+PTx 1.2% rats despite lower PTH and FGF23 levels than in sham group. These biochemical changes were accompanied by a decrease in bone formation rates. The Nx+PTx 1.2% group had lower bone volume (BV/TV), higher osteoblast and osteocyte apoptosis, and higher SOST and Dickkopf-1 gene expression than the Nx+PTx 0.6% group. Nx+PTx 0.6% rat had very low serum sclerostin levels, and Nx+PTx 1.2% had intermediate sclerostin levels compared with sham group. Finally, there was a negative correlation between BV/TV and serum sclerostin. These results suggest that high dietary phosphate intake decreases bone volume in an experimental model of CKD-ABD, possibly via changes in SOST expression through a PTH-independent mechanism. These findings could have relevance for the clinical setting of CKD-ABD in patients who low turnover bone disease might be attenuated by optimal control of phosphate intake and/or absorption.
format	article
author	Juliana C Ferreira Guaraciaba O Ferrari Katia R Neves Raquel T Cavallari Wagner V Dominguez Luciene M Dos Reis Fabiana G Graciolli Elizabeth C Oliveira Shiguang Liu Yves Sabbagh Vanda Jorgetti Susan Schiavi Rosa M A Moysés
author_facet	Juliana C Ferreira Guaraciaba O Ferrari Katia R Neves Raquel T Cavallari Wagner V Dominguez Luciene M Dos Reis Fabiana G Graciolli Elizabeth C Oliveira Shiguang Liu Yves Sabbagh Vanda Jorgetti Susan Schiavi Rosa M A Moysés
author_sort	Juliana C Ferreira
title	Effects of dietary phosphate on adynamic bone disease in rats with chronic kidney disease--role of sclerostin?
title_short	Effects of dietary phosphate on adynamic bone disease in rats with chronic kidney disease--role of sclerostin?
title_full	Effects of dietary phosphate on adynamic bone disease in rats with chronic kidney disease--role of sclerostin?
title_fullStr	Effects of dietary phosphate on adynamic bone disease in rats with chronic kidney disease--role of sclerostin?
title_full_unstemmed	Effects of dietary phosphate on adynamic bone disease in rats with chronic kidney disease--role of sclerostin?
title_sort	effects of dietary phosphate on adynamic bone disease in rats with chronic kidney disease--role of sclerostin?
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/781980599bad4e779c03aaa75fd55bd1
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Effects of dietary phosphate on adynamic bone disease in rats with chronic kidney disease--role of sclerostin?

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