Elevated FGF23 and disordered renal mineral handling with reduced bone mineralization in chronically erythropoietin over-expressing transgenic mice

Autor:	Carla Bettoni, Petra Seebeck, Arezoo Daryadel, Carsten A. Wagner, Udo Schnitzbauer, Max Gassmann, Luciano Natale
Přispěvatelé:	University of Zurich, Wagner, Carsten A
Jazyk:	angličtina
Rok vydání:	2019
Předmět:	0301 basic medicine Fibroblast growth factor 23 Deoxypyridinoline lcsh:Medicine Kidney urologic and male genital diseases Bone remodeling 10052 Institute of Physiology Mice chemistry.chemical_compound 0302 clinical medicine Bone Density Homeostasis Hypercalciuria Amino Acids lcsh:Science Minerals Osteomalacia Multidisciplinary 10081 Institute of Veterinary Physiology 10076 Center for Integrative Human Physiology Female medicine.drug medicine.medical_specialty Calcitriol Osteocalcin Calcium and vitamin D Mice Transgenic 030209 endocrinology & metabolism 610 Medicine & health Article Phosphates 03 medical and health sciences Calcification Physiologic Internal medicine medicine Animals Renal Insufficiency Chronic Erythropoietin 1000 Multidisciplinary lcsh:R medicine.disease Fibroblast Growth Factors Mice Inbred C57BL Fibroblast Growth Factor-23 030104 developmental biology Endocrinology chemistry 570 Life sciences biology Calcium lcsh:Q Renal phosphate excretion
Zdroj:	Scientific Reports, Vol 9, Iss 1, Pp 1-13 (2019) Scientific Reports
ISSN:	2045-2322
DOI:	10.1038/s41598-019-51577-z
Popis:	Fibroblast Growth Factor 23 (FGF23) is a phosphaturic factor causing increased renal phosphate excretion as well as suppression of 1,25 (OH)2-vitamin D3. Highly elevated FGF23 can promote development of rickets and osteomalacia. We and others previously reported that acute application of erythropoietin (EPO) stimulates FGF23 production. Considering that EPO is clinically used as chronic treatment against anemia, we used here the Tg6 mouse model that constitutively overexpresses human EPO in an oxygen-independent manner, to examine the consequences of long-term EPO therapy on mineral and bone metabolism. Six to eight weeks old female Tg6 mice showed elevated intact and C-terminal fragment of FGF23 but normal plasma levels of PTH, calcitriol, calcium and phosphate. Renal function showed moderate alterations with higher urea and creatinine clearance and mild albuminuria. Renal phosphate excretion was normal whereas mild hypercalciuria was found. Renal expression of the key proteins TRPV5 and calbindin D28k involved in active calcium reabsorption was reduced in Tg6 mice. Plasma levels of the bone turnover marker osteocalcin were comparable between groups. However, urinary excretion of deoxypyridinoline (DPD) was lower in Tg6 mice. MicroCT analysis showed reduced total, cortical, and trabecular bone mineral density in femora from Tg6 mice. Our data reveal that chronic elevation of EPO is associated with high FGF23 levels and disturbed mineral homeostasis resulting in reduced bone mineral density. These observations imply the need to study the impact of therapeutically applied EPO on bone mineralization in patients, especially those suffering from chronic kidney disease.
Databáze:	OpenAIRE
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