Current Molecular Biology Reports

, Volume 5, Issue 1, pp 8–17 | Cite as

Regulation of Fibroblast Growth Factor 23 by Iron, EPO, and HIF

  • Jonathan A. Wheeler
  • Erica L. ClinkenbeardEmail author
Molecular Control of Phosphorus Homeostasis (B van der Eerden, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Molecular Control of Phosphorus Homeostasis


Purpose of Review

Fibroblast growth factor-23 (FGF23) is the key hormone produced in bone critical for phosphate homeostasis. Elevated serum phosphorus and 1,25-dihydroxyvitamin D stimulates FGF23 production to promote renal phosphate excretion and decrease 1,25-dihydroxyvitamin D synthesis, thus completing the feedback loop and suppressing FGF23. Unexpectedly, studies of common and rare heritable disorders of phosphate handling identified links between iron and FGF23 demonstrating novel regulation outside the phosphate pathway.

Recent Findings

Iron deficiency combined with an FGF23 cleavage mutation was found to induce the autosomal dominant hypophosphatemic rickets phenotype. Physiological responses to iron deficiency, such as erythropoietin production as well as hypoxia inducible factor activation, have been indicated in regulating FGF23. Additionally, specific iron formulations, used to treat iron deficiency, alter post-translational processing thereby shifting FGF23 protein secretion.


Molecular and clinical studies revealed that iron deficiency, through several mechanisms, alters FGF23 at the transcriptional and post-translational level. This review will focus upon the novel discoveries elucidated between iron, its regulators, and their influence on FGF23 bioactivity.


FGF-23 Iron Erythropoietin Phosphate Hypoxia-inducible factor 


Funding Information

The authors would like to acknowledge NIH grants F32-AR065389 (ELC); the Comprehensive Training Program in Musculoskeletal Research Grant T32-AR065971 (JAW) and a Center for Translational Sciences Institutional Biomedical Research Grant (ELC).

Compliance with Ethical Standards

Conflict of Interest

Jonathan A. Wheeler and Erica L. Clinkenbeard each declare no potential conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Medical and Molecular GeneticsIndiana University School of MedicineIndianapolisUSA
  2. 2.Department of Medical and Molecular GeneticsIndiana University School of MedicineIndianapolisUSA

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