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


RESULTS
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.


CONCLUSIONS
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.
Liu
Shiguang
S
Department of Internal Medicine, The Kidney Institute and Division of Nephrology, Kansas City, Kansas 66160, USA.
Gupta
Aditi
A
Quarles
L Darryl
LD
D000818:Animals; D001842:Bone and Bones / Q000502:physiology*; D002113:Calcification, Physiologic / Q000187:drug effects; D005109:Extracellular Matrix / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000502:physiology; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000502:physiology*; D006023:Glycoproteins / Q000502:physiology; D006706:Homeostasis; D006801:Humans; D017674:Hypophosphatemia / Q000209:etiology; D007668:Kidney / Q000502:physiology*; D051379:Mice; D010281:Parathyroid Hormone / Q000502:physiology; D010710:Phosphates / Q000652:urine; D010750:Phosphoproteins / Q000502:physiology; D017468:Receptors, Fibroblast Growth Factor / Q000502:physiology; D014807:Vitamin D / Q000031:analogs & derivatives / Q000502:physiology
C513309:DMP1 protein, human; D016326:Extracellular Matrix Proteins; C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; D006023:Glycoproteins; C486579:MEPE protein, human; D010281:Parathyroid Hormone; D010710:Phosphates; D010750:Phosphoproteins; D017468:Receptors, Fibroblast Growth Factor; D014807:Vitamin D; D005346:Fibroblast Growth Factors; C097949:1,25-dihydroxyvitamin D; D000089703:Fibroblast Growth Factor-23