S24-1 FGF23 Regulation and Function: Lessons from Murine Models

Program: Symposia
Session: S24-FGF23: New Insight on Regulation in Humans and Murine Models
Sunday, June 16, 2013: 9:00 AM-10:30 AM
Presentation Start Time: 9:00 AM
Room 102 (Moscone Center)
L Darryl Quarles*
University of Tennessee Health Science Center, Memphis, TN
Talk Description:

FGF-23 is produced and 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. Mouse genetic models have established the central role of secreted FGF-23 in complex endocrine networks that are regulated by local bone-derived factors involved in mineralization of extracellular matrix. Inactivating mutations of genes that play a role in the mineralization of extracellular matrix, including PHEX, DMP1, FAM20C, Ank 1and ENPP1, result in a common phenotype characterized by elevations in FGF-23 production by bone and consequent hypophosphatemia, suppression of 1,25(OH)2D and defects in bone mineralization. The mechanisms whereby these distinct mutations lead to the stimulation of FGF23 gene transcription in osteoblasts and osteocytes are at least in part, through activation of FGFR1-dependent pathways. These FGF-23 regulatory pathways may enable systemic phosphate and vitamin D homeostasis to be coordinated with bone mineralization.

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