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The PTH-Vitamin D-FGF23 axis

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Abstract

Fibroblast growth factor 23 (FGF23) has emerged as an important regulator of phosphate and vitamin D homeostasis. It is important to understand how FGF23 interacts with vitamin D and parathyroid hormone (PTH) in a FGF23-Vitamin D-PTH axis to regulate mineral homeostasis. In this review, we discuss the genomic structure, and transcriptional, translational, and posttranslational regulation of FGF23. We describe its interaction with PTH and vitamin D, disorders of altered FGF23 states, and emerging therapies for diseases of FGF23 based upon these findings. This discussion helps redefine the role of PTH and vitamin D in relation to a complex bone-kidney-parathyroid loop, and points to areas within this complicated field in need of further clarification and research.

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Abbreviations

PTH:

Parathyroid hormone

FGF23:

Fibroblast growth factor-23

TIO:

Tumor induced osteomalacia

1,25-D:

1,25 dihydroxyvitamin D3

XLH:

X-linked hypophosphatemic rickets

ADHR:

Autosomal dominant hypophosphatemic rickets

αKl:

α-klotho

CKD:

Chronic kidney disease

FGFR:

FGF receptor

SPC:

Subtilisin-like proprotein convertase

GALNT3:

O-glycosylation through ppGalNAc-T3

NaPi:

Sodium-phosphate co-transporter

P-ERK:

Phosphate epidermal growth factor

EGR-1:

Early growth response gene 1

G-CK:

Golgi casein kinase

FD:

Fibrous dysplasia

VDR:

Vitamin D receptor

HYP:

X-linked hypophosphatemic rickets mice

MEPE:

Matrix extracellular phosphoglycoprotein

ASARM:

Acidic serine aspartate-rich matrix extracellular phosphoglycoprotein (MEPE)-associated motif

PHEX:

Phosphate regulating endopeptidase homolog, X-linked

FN1:

Fibronectin 1

HFTC/HHS:

Hyperphosphatemic familial tumoral calcinosis/hyperostosis syndrome

eGFR:

Estimated glomerular filtration rate

LVH:

Left ventricular hypertrophy

FAM20C:

Kinase family with sequence similarity 20, member C

ENPP-1:

Ectonucleotide pyrophosphatase/phosphodiesterase 1

DMP-1:

Dentin matrix protein-1

OGD:

Osteoglophonic dysplasia

FN1:

Fibronectin 1

FISH:

Fluorescence in situ hybridization

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Acknowledgments

This research was supported by the Division of Intramural Research, National Institute of Dental and Craniofacial Research, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services.

Conflict of Interest

JEB and MTC have no conflicts of interest.

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Authors and Affiliations

  1. Program of Reproductive and Adult Endocrinology, National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, MD, 20892, USA

    Jenny E. Blau

  2. Skeletal Clinical Studies Unit, Craniofacial and Skeletal Disease Branch, National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health, Bethesda, MD, 20892, USA

    Michael T. Collins

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Blau, J.E., Collins, M.T. The PTH-Vitamin D-FGF23 axis. Rev Endocr Metab Disord 16, 165–174 (2015). https://doi.org/10.1007/s11154-015-9318-z

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