Calcium and phosphate homeostasis: concerted interplay of new regulators.
Calcium (Ca(2+)) and phosphate (P(i)) are essential to many vital physiological processes. Consequently the maintenance of Ca(2+) and P(i) homeostasis is essential to a healthy existence. This occurs through the concerted action of intestinal, renal, and skeletal regulatory mechanisms. Ca(2+) and P(i) handling by these organs is under tight hormonal control. Disturbances in their homeostasis have been linked to pathophysiological disorders including chronic renal insufficiency, kidney stone formation, and bone abnormalities. Importantly, the kidneys fine-tune the amount of Ca(2+) and P(i) retained in the body by altering their (re)absorption from the glomerular filtrate. The ion transport proteins involved in this process have been studied extensively. Recently, new key players have been identified in the regulation of the Ca(2+) and P(i) balance. Novel regulatory mechanisms and their implications were introduced for the antiaging hormone klotho and fibroblast growth factor member 23 (FGF23). Importantly, transgenic mouse models, exhibiting disturbances in Ca(2+) and P(i) balance, have been of great value in the elucidation of klotho and FGF23 functioning. This review highlights the current knowledge and ongoing research into Ca(2+) and P(i) homeostasis, emphasizing findings from several relevant knockout mouse models.
Renkema
Kirsten Y
KY
Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Alexander
R Todd
RT
Bindels
René J
RJ
Hoenderop
Joost G
JG
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism; D000818:Animals; D002116:Calcitonin / Q000378:metabolism; D002117:Calcitriol / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology; D002128:Calcium Metabolism Disorders / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005966:Glucuronidase / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D000090265:Klotho Proteins; D051379:Mice; D018345:Mice, Knockout; D010281:Parathyroid Hormone / Q000378:metabolism; D028061:Phosphate Transport Proteins / Q000502:physiology; D010710:Phosphates / Q000378:metabolism*; D010760:Phosphorus Metabolism Disorders / Q000378:metabolism; D044169:Receptors, Calcium-Sensing / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000503:physiopathology; D050916:TRPV Cation Channels / Q000502:physiology; D020840:Tissue Kallikreins / Q000378:metabolism
D015220:Calcium Channels; D004967:Estrogens; C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; D010281:Parathyroid Hormone; D028061:Phosphate Transport Proteins; D010710:Phosphates; D044169:Receptors, Calcium-Sensing; D050916:TRPV Cation Channels; C492240:Trpv5 protein, mouse; C446923:Trpv6 protein, mouse; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002116:Calcitonin; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D005966:Glucuronidase; D000090265:Klotho Proteins; D020840:Tissue Kallikreins; D002117:Calcitriol; D002118:Calcium