Emerging role of fibroblast growth factor 23 in a bone-kidney axis regulating systemic phosphate homeostasis and extracellular matrix mineralization.

Abstract

PURPOSE OF REVIEW:

To describe emerging understanding of fibroblast growth factor 23 (FGF23) - a bone-derived hormone that inhibits phosphate reabsorption and calcitriol production by kidney and participates as the principle phosphaturic factor in a bone-kidney axis coordinating systemic phosphate homeostasis and bone mineralization.

RECENT FINDINGS:

FGF23 (a circulating factor made by osteocytes in bone) inhibits phosphate reabsorption and 1,25(OH)2D production by kidney. Physiologically, FGF23 is a counter-regulatory phosphaturic hormone for vitamin D and coordinates systemic phosphate homeostasis with skeletal mineralization. Pathologically, high circulating FGF23 levels cause hypophosphatemia, decreased 1,25(OH)2D production, elevated parathyroid hormone and rickets/osteomalacia. FGF23 mutations impairing its degradation cause autosomal dominant hypophosphatemic rickets. Respective loss-of-function mutations of osteocyte gene products DMP1 and Phex cause autosomal recessive hypophosphatemic rickets and X-linked hypophosphatemic rickets, initiating increased FGF23 production. Low FGF23 levels lead to hyperphosphatemia, elevated 1,25(OH)2D, and soft-tissue calcifications. FGF23 is markedly increased in chronic renal disease, but its role remains undefined.

SUMMARY:

FGF23 discovery has uncovered primary regulatory pathways and new systems biology governing bone mineralization, vitamin D metabolism, parathyroid gland function, and renal phosphate handling. FGF23 assessment will become important in diagnosing hypophosphatemic and hyperphosphatemic disorders, for which pharmacological regulation of FGF23 levels may provide novel treatments.

• Authors: Shiguang Liu, Aditi Gupta, L Darryl Quarles
• Journal: Current opinion in nephrology and hypertension (Curr Opin Nephrol Hypertens) Vol. 16 Issue 4 Pg. 329-35 (Jul 2007) ISSN: 1062-4821 [Print] England
• PMID: 17565275 (Publication Type: Journal Article, Review)

Chemical References

• DMP1 protein, human
• Extracellular Matrix Proteins
• FGF23 protein, human
• Fgf23 protein, mouse
• Glycoproteins
• MEPE protein, human
• Parathyroid Hormone
• Phosphates
• Phosphoproteins
• Receptors, Fibroblast Growth Factor
• Vitamin D
• Fibroblast Growth Factors
• 1,25-dihydroxyvitamin D
• Fibroblast Growth Factor-23

Topics

• Animals
• Bone and Bones (physiology)
• Calcification, Physiologic (drug effects)
• Extracellular Matrix (physiology)
• Extracellular Matrix Proteins (physiology)
• Fibroblast Growth Factor-23
• Fibroblast Growth Factors (physiology)
• Glycoproteins (physiology)
• Homeostasis
• Humans
• Hypophosphatemia (etiology)
• Kidney (physiology)
• Mice
• Parathyroid Hormone (physiology)
• Phosphates (urine)
• Phosphoproteins (physiology)
• Receptors, Fibroblast Growth Factor (physiology)
• Vitamin D (analogs & derivatives, physiology)