Mineral metabolism and aging: the fibroblast growth factor 23 enigma.
OBJECTIVE
The regulation of phosphate homeostasis was thought to be passively mediated by the calciotrophic hormones parathyroid hormone and 1,25(OH)2D3. This article summarizes the emerging trends that show an active regulation of phosphate homeostasis by fibroblast growth factor 23 (FGF-23) - a process fairly independent of calcium homeostasis - and how altered mineral ion metabolism may affect the aging process.


RESULTS
A major breakthrough in FGF-23 biology has been achieved by the demonstration of strikingly similar physical/biochemical phenotypes of Fgf-23(-/-) and klotho hypomorph mice, which eventually led to the identification of klotho as a cofactor in FGF-23 and its receptor interactions. Furthermore, FGF-23 has emerged as a counter regulator of the renal 1alpha(OH)ase and sodium-phosphate cotransporter activities to modulate phosphate homeostasis. Finally, studies point towards a role of dentine matrix protein 1 in affecting phosphate homeostasis, in coordination with FGF-23.


CONCLUSIONS
Recent mouse genetic studies have broadened our understanding of biochemical/molecular pathways involved in phosphate homeostasis, and linked FGF-23 to such regulation. Understanding the molecular interactions of essential calcium and phosphate regulators will enhance our knowledge of the coordinated regulation of mineral ion metabolism, and will help to redefine the molecular pathology of age-associated lesions accompanied by abnormal mineral ion metabolism such as vascular calcifications and osteoporosis.
Lanske
Beate
B
Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts 02115, USA. beate_lanske@hsdm.harvard.edu
Razzaque
M Shawkat
MS
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism; D000368:Aged; D000375:Aging / Q000502:physiology*; D000818:Animals; D002114:Calcinosis / Q000209:etiology; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000378:metabolism*; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000502:physiology*; D005966:Glucuronidase / Q000502:physiology; D006706:Homeostasis; D006801:Humans; D000090265:Klotho Proteins; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008954:Models, Biological; D010710:Phosphates / Q000097:blood; D010760:Phosphorus Metabolism Disorders / Q000150:complications; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa / Q000502:physiology
C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; D010710:Phosphates; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D005966:Glucuronidase; D000090265:Klotho Proteins; D002117:Calcitriol; D002118:Calcium