ESPE Abstracts (2016) 86 WG4.5

FGF23, Klotho and PTH in the Regulation of Mineral Homeostasis

Thomas Carpenter


Background: The Fibroblast Growth Factors (FGFs) are a large family of proteins including paracrine, intracrine, and endocrine FGFs. Paracrine and endocrine FGFs interact with specific cell surface receptors (FGFRs) that, via intracellular tyrosine kinase activity, initiate a cascade of downstream intracellular events. Specificity of paracrine/autocrine FGF activity is provided locally by the local production of these FGFs and their cognate receptors. In contrast, endocrine FGFs, such as FGF23, generally require a coreceptor, alpha- or beta-klotho, to effectively bind to their respective target cells. Thus endocrine FGFs target activity to tissues that express klotho. The discovery of FGF23 and its unusual role has brought to attention a novel understanding of mammalian mineral homeostasis, and important clues to the mediation of disorders of hypo- and hyper-phosphatemia.

Conclusion: FGF23, its receptor(s), Klotho, and vitamin D serve as part of an interconnected system for the multifaceted regulation of calcium and phosphate homeostasis. Such a system is advantageous for appropriate management of mineral needs in times of limited supply, overabundance, and for the changing needs of the vertebrate skeleton. Disruption of the system can lead to a variety of disorders of bone and mineral metabolism, and pharmacologic targeting of the system should provide a productive strategy for the treatment of some of these disorders.

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