Skeletal secretion of FGF-23 regulates phosphate and vitamin D metabolism

Research output: Contribution to journalReview article

135 Citations (Scopus)

Abstract

The discovery of fibroblast growth factor 23 (FGF-23) has expanded our understanding of phosphate and vitamin D homeostasis and provided new insights into the pathogenesis of hereditary hypophosphatemic and hyperphosphatemic disorders, as well as acquired disorders of phosphate metabolism, such as chronic kidney disease. FGF-23 is secreted by osteoblasts and osteocytes in bone and principally targets the kidney to regulate the reabsorption of phosphate, the production and catabolism of 1,25-dihydroxyvitamin D and the expression of α-Klotho, an anti-ageing hormone. Secreted FGF-23 plays a central role in complex endocrine networks involving local bone-derived factors that regulate mineralization of extracellular matrix and systemic hormones involved in mineral metabolism. Inactivating mutations of PHEX, DMP1 and ENPP1, which cause hereditary hypophosphatemic disorders and primary defects in bone mineralization, stimulate FGF23 gene transcription in osteoblasts and osteocytes, at least in part, through canonical and intracrine FGF receptor pathways. These FGF-23 regulatory pathways may enable systemic phosphate and vitamin D homeostasis to be coordinated with bone mineralization. FGF-23 also functions as a counter-regulatory hormone for 1,25-dihydroxyvitamin D in a bone-kidney endocrine loop. FGF-23, through regulation of additional genes in the kidney and extrarenal tissues, probably has broader physiological functions beyond regulation of mineral metabolism that account for the association between FGF-23 and increased mortality and morbidity in chronic kidney disease.

Original languageEnglish (US)
Pages (from-to)276-286
Number of pages11
JournalNature Reviews Endocrinology
Volume8
Issue number5
DOIs
StatePublished - May 1 2012

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Vitamin D
Phosphates
Osteocytes
Physiologic Calcification
Hormones
Osteoblasts
Chronic Renal Insufficiency
Kidney
Bone and Bones
Minerals
Homeostasis
Fibroblast Growth Factor Receptors
fibroblast growth factor 23
Genes
Extracellular Matrix
Morbidity
Mutation
Mortality

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Skeletal secretion of FGF-23 regulates phosphate and vitamin D metabolism. / Quarles, Leigh.

In: Nature Reviews Endocrinology, Vol. 8, No. 5, 01.05.2012, p. 276-286.

Research output: Contribution to journalReview article

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