title: [Classical actions of vitamin D: insights from human genetics and from mouse models on calcium and phosphate homeostasis].
abstract: At the beginning of the 20th century, the discovery of vitamin D by Sir EV McCollum allowed a better comprehension of its origin and its role, and made it possible to cure rickets, a largely prevalent disease at that time. The main role of vitamin D3 is to maintain calcium and phosphate homeostasis through the action of 1,25-dihydroxyvitamin D3, its active form. This underlies physiological functions related to calcium and phosphate, such as bone mineralization or muscle function. Progress in basic research for the last 40 years led to the discovery of the main hydroxylation steps that produce and catabolize the active form of vitamin D. It also uncovered the molecular aspects of vitamin D action, from its nuclear receptor, VDR, to the various target genes of this hormone. Recent progress in human genetics pointed out mutations in genes involved in vitamin D metabolism and 1,25-dihydroxyvitamin D3 actions. It also helped to understand the role of the major actors that control vitamin D production and effects, through 1,25-dihydroxyvitamin D3 actions on phosphate and calcium homeostasis, and on bone biology. Genetical engineering targeting the whole animal or defined tissues or cell types have yielded many mouse models in the past decades. When targeted to tissues important for vitamin D metabolism and activity, these models allowed a more detailed comprehension of vitamin effects on calcium and phosphorus homeostasis.
authors.affiliation: INSERM U1132, Hôpital Lariboisière, 75010 Paris, France - Université Paris Diderot, Sorbonne Paris Cité, 75013 Paris, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Jehan
authors.affiliation: Université de Médecine et de Pharmacie "Nicolae Testemitanu", Chisinau, Moldavie.
authors.forename: Alexandru
authors.initials: A
authors.lastname: Voloc
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D006801:Humans; D007408:Intestinal Absorption / Q000235:genetics / Q000502:physiology; D007668:Kidney / Q000503:physiopathology; D051379:Mice; D023421:Models, Animal; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology; D010280:Parathyroid Glands / Q000503:physiopathology; D010710:Phosphates / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000502:physiology; D012279:Rickets / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D050916:TRPV Cation Channels / Q000172:deficiency / Q000235:genetics; D014807:Vitamin D / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000502:physiology*; D014808:Vitamin D Deficiency / Q000235:genetics / Q000378:metabolism
chemical_list: D010710:Phosphates; D018167:Receptors, Calcitriol; D050916:TRPV Cation Channels; C120776:TRPV6 channel; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; D003577:Cytochrome P-450 Enzyme System; D002118:Calcium