High-serum phosphate and parathyroid hormone distinctly regulate bone loss and vascular calcification in experimental chronic kidney disease

被引：55

作者：

Carrillo-Lopez, Natalia ^{[1
]}

Panizo, Sara ^{[1
]}

Alonso-Montes, Cristina ^{[1
]}

Martinez-Arias, Laura ^{[1
]}

Avello, Noelia ^{[2
]}

Sosa, Patricia ^{[3
]}

Dusso, Adriana S. ^{[1
]}

Cannata-Andia, Jorge B. ^{[1
,4
]}

Naves-Diaz, Manuel ^{[1
]}

机构：

[1] Hosp Univ Cent Asturias, Inst Invest Sanitaria Principado Asturias ISPA, Bone & Mineral Res Unit, REDinREN ISCIII, Oviedo, Spain

[2] Hosp Univ Cent Asturias, Lab Med, Oviedo, Spain

[3] Univ Alcala, REDinREN ISCIII, Dept Biol Sistemas, Alcala De Henares, Spain

[4] Univ Oviedo, Dept Med, Oviedo, Spain

来源：

NEPHROLOGY DIALYSIS TRANSPLANTATION | 2019年 / 34卷 / 06期

关键词：

gene expression; mineral metabolism; parathyroidectomy; renal osteodystrophy; vascular calcification; CIRCULATING LEVELS; RAT MODEL; CALCIUM; PHOSPHORUS; SCLEROSTIN; EXPRESSION;

D O I：

10.1093/ndt/gfy287

中图分类号：

R3 [基础医学]; R4 [临床医学];

学科分类号：

1001 ; 1002 ; 100602 ;

摘要：

Background In chronic kidney disease (CKD), increases in serum phosphate and parathyroid hormone (PTH) aggravate vascular calcification (VC) and bone loss. This study was designed to discriminate high phosphorus (HP) and PTH contribution to VC and bone loss. Methods Nephrectomized rats fed a HP diet underwent either sham operation or parathyroidectomy and PTH 1-34 supplementation to normalize serum PTH. Results In uraemic rats fed a HP diet, parathyroidectomy with serum PTH 1-34 supplementation resulted in (i) reduced aortic calcium (80%) by attenuating osteogenic differentiation (higher -actin; reduced Runx2 and BMP2) and increasing the Wnt inhibitor Sclerostin, despite a similar degree of hyperphosphataemia, renal damage and serum Klotho; (ii) prevention of bone loss mostly by attenuating bone resorption and increases in Wnt inhibitors; and (iii) a 70% decrease in serum calcitriol levels despite significantly reduced serum Fgf23, calcium and renal 24-hydroxylase, which questions that Fgf23 is the main regulator of renal calcitriol production. Significantly, when vascular smooth muscle cells (VSMCs) were exposed exclusively to high phosphate and calcium, high PTH enhanced while low PTH attenuated calcium deposition through parathyroid hormone 1 receptor (PTH1R) signalling. Conclusions In hyperphosphataemic CKD, a defective suppression of high PTH exacerbates HP-mediated osteogenic VSMC differentiation and reduces vascular levels of anti-calcifying sclerostin.

引用

页码：934 / 941

页数：8