Beate Lanske1, M Shawkat Razzaque. 1. Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts 02115, USA. beate_lanske@hsdm.harvard.edu
Abstract
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.
Authors: Philippe H Tartaix; Marie Doulaverakis; Anne George; Larry W Fisher; William T Butler; Chunlin Qin; Erdjan Salih; Melin Tan; Yukiji Fujimoto; Lyudmila Spevak; Adele L Boskey Journal: J Biol Chem Date: 2004-02-09 Impact factor: 5.157
Authors: R J Heikinheimo; J A Inkovaara; E J Harju; M V Haavisto; R H Kaarela; J M Kataja; A M Kokko; L A Kolho; S A Rajala Journal: Calcif Tissue Int Date: 1992-08 Impact factor: 4.333
Authors: Quan Yuan; Tadatoshi Sato; Michael Densmore; Hiroaki Saito; Christiane Schüler; Reinhold G Erben; Beate Lanske Journal: J Bone Miner Res Date: 2011-09 Impact factor: 6.741
Authors: S DeLuca; D Sitara; K Kang; R Marsell; K Jonsson; T Taguchi; R G Erben; M S Razzaque; B Lanske Journal: J Pathol Date: 2008-11 Impact factor: 7.996