Mineral metabolism and aging: the fibroblast growth factor 23 enigma
- 1 July 2007
- journal article
- review article
- Published by Ovid Technologies (Wolters Kluwer Health) in Current Opinion in Nephrology and Hypertension
- Vol. 16 (4), 311-318
- https://doi.org/10.1097/mnh.0b013e3281c55eca
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 1α(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.Keywords
This publication has 75 references indexed in Scilit:
- Vitamin D and aging: old concepts and new insightsThe Journal of Nutritional Biochemistry, 2007
- The emerging role of the fibroblast growth factor-23–klotho axis in renal regulation of phosphate homeostasisJournal of Endocrinology, 2007
- Premature aging in klotho mutant mice: Cause or consequence?Ageing Research Reviews, 2007
- Molecular Insights into the Klotho-Dependent, Endocrine Mode of Action of Fibroblast Growth Factor 19 Subfamily MembersMolecular and Cellular Biology, 2007
- Genetic Ablation of Vitamin D Activation Pathway Reverses Biochemical and Skeletal Anomalies in Fgf-23-Null AnimalsThe American Journal of Pathology, 2006
- Klotho converts canonical FGF receptor into a specific receptor for FGF23Nature, 2006
- Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolismNature Genetics, 2006
- Calcium plus Vitamin D Supplementation and the Risk of FracturesNew England Journal of Medicine, 2006
- FGF-23 Is a Potent Regulator of Vitamin D Metabolism and Phosphate HomeostasisJournal of Bone and Mineral Research, 2004
- Identification of a Novel Fibroblast Growth Factor, FGF-23, Preferentially Expressed in the Ventrolateral Thalamic Nucleus of the BrainBiochemical and Biophysical Research Communications, 2000