title: Osteo-renal cross-talk and phosphate metabolism by the FGF23-Klotho system.
abstract: Phosphate is widely distributed in the body and an adequate balance is required for maintaining essential cellular and organ functions. Dysregulation of phosphate balance, either in the form of hypophosphatemia or hyperphosphatemia can induce disorders ranging from rickets/osteomalacia to cardiovascular calcification. A physiologic phosphate balance is delicately maintained by multiorgan cross-talks among the intestine, kidney, and bone. Sodium-dependent phosphate (Na/Pi) cotransporters present in the intestine and kidney play a major role in phosphate absorption and reabsorption, according to the body's demand. Some of the calcium regulating factors, including parathyroid hormone and vitamin D can influence the activities of Na/Pi cotransporters, and thereby can affect phosphate balance. In addition, molecular analysis of the unexplained hypophosphatemic diseases, including autosomal-dominant hypophosphatemic rickets and tumor-induced osteomalacia has led to the identification of fibroblast growth factor 23 (FGF23). Subsequent studies have documented that bone-derived FGF23 and kidney-derived klotho can form an endocrine network to control urinary phosphate excretion. Studies have also documented negative effect of FGF23/klotho system on vitamin D metabolism and Na/Pi cotransporter activities. This article will summarize how the FGF23/klotho system might influence systemic phosphate metabolism, and consequences of its abnormal regulation will be briefly described.
authors: Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA 02115, USA.
authors: Mutsuko
authors: M
authors: Ohnishi
authors: Mohammed S
authors: MS
authors: Razzaque
mesh_terms: D000136:Acid-Base Equilibrium / Q000502:physiology; D000818:Animals; D016723:Bone Remodeling; D001842:Bone and Bones / Q000378:metabolism*; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000209:etiology / Q000378:metabolism; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000502:physiology*; D005966:Glucuronidase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006801:Humans; D054559:Hyperphosphatemia / Q000378:metabolism; D017674:Hypophosphatemia / Q000378:metabolism; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D007674:Kidney Diseases / Q000150:complications / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism*; D000090265:Klotho Proteins; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D010018:Osteomalacia / Q000209:etiology / Q000378:metabolism; D010257:Paraneoplastic Syndromes / Q000378:metabolism; D010281:Parathyroid Hormone / Q000502:physiology; D010710:Phosphates / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D050608:Sodium-Phosphate Cotransporter Proteins / Q000378:metabolism; D014807:Vitamin D / Q000502:physiology
chemical_list: C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; D010281:Parathyroid Hormone; D010710:Phosphates; D050608:Sodium-Phosphate Cotransporter Proteins; D014807:Vitamin D; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins