title: Vitamin D metabolism, cartilage and bone fracture repair.
abstract: The 1,25-(OH)(2)D metabolite mediates the endocrine actions of vitamin D by regulating in the small intestine the expression of target genes that play a critical role in intestinal calcium absorption. The major role of the vitamin D hormone on bone is indirect and mediated through its endocrine function on mineral homeostasis. However, genetic manipulation of the expression of Cyp27b1 or the VDR in chondrocytes strongly support a direct role for locally synthesized 1,25(OH)(2)D, acting through the VDR, in vascular invasion and osteoclastogenesis during endochondral bone development. Cells from the growth plate respond to the 24,25-(OH)(2)D and 1,25-(OH)(2)D metabolites in a cell maturation-dependent manner and the effects of 1,25-(OH)(2)D are thought to be mediated through binding to the membrane-associated receptor PDIA3 (protein disulfide isomerase associated 3). The physiological relevance of membrane-mediated 1,25-(OH)(2)D signaling is emerging and is discussed. Finally, preliminary results suggest that mice deficient for Cyp24a1 exhibit a delay in bone fracture healing and support a role for 24,25-(OH)(2)D in mammalian fracture repair.
authors.affiliation: Genetics Unit, Shriners Hospital for Children, Montreal, Quebec, Canada H3G 1A6. rst-arnaud@shriners.mcgill.ca
authors.forename: René
authors.initials: R
authors.lastname: St-Arnaud
authors.forename: Roy Pascal
authors.initials: RP
authors.lastname: Naja
mesh_terms: D000818:Animals; D001846:Bone Development / Q000502:physiology; D001842:Bone and Bones / Q000378:metabolism*; D002356:Cartilage / Q000378:metabolism*; D019902:Chondrocytes / Q000378:metabolism*; D017102:Fracture Healing / Q000187:drug effects / Q000235:genetics; D050723:Fractures, Bone / Q000378:metabolism*; D006801:Humans; D051379:Mice; D015398:Signal Transduction; D014807:Vitamin D / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D014807:Vitamin D