title: Vitamin D action and regulation of bone remodeling: suppression of osteoclastogenesis by the mature osteoblast.
abstract: Vitamin D acts through the immature osteoblast to stimulate osteoclastogenesis. Transgenic elevation of VDR in mature osteoblasts was found to inhibit osteoclastogenesis associated with an altered OPG response. This inhibition was confined to cancellous bone. This study indicates that vitamin D-mediated osteoclastogenesis is regulated locally by OPG production in the mature osteoblast.
  
  
  BACKGROUND
  Vitamin D stimulates osteoclastogenesis acting through its nuclear receptor (VDR) in immature osteoblast/stromal cells. This mobilization of calcium stores does not occur in a random manner, with bone preferentially removed from cancellous bone. The process whereby the systemic, humoral regulator is targeted to a particular region of the skeleton is unclear.
  
  
  METHODS
  Bone resorption was assessed in mice with vitamin D receptor transgenically elevated in mature osteoblasts (OSVDR). Vitamin D-mediated osteoclastogenesis was examined in vitro using OSVDR osteoblasts and osteoblastic RANKL: osteoprotegerin (OPG) examined in vivo and in vitro after vitamin D treatment.
  
  
  RESULTS
  Vitamin D-mediated osteoclastogenesis was reduced in OSVDR mice on chow and calcium-restricted diets, with effects confined to cancellous bone. OSVDR osteoblasts had a reduced capacity to support osteoclastogenesis in culture. The vitamin D-mediated reduction in OPG expression was reduced in OSVDR osteoblasts in vivo and in vitro, resulting in a reduced RANKL/OPG ratio in OSVDR compared with wildtype, after exposure to vitamin D.
  
  
  CONCLUSIONS
  Mature osteoblasts play an inhibitory role in bone resorption, with active vitamin D metabolites acting through the VDR to increase OPG. This inhibition is less active in cancellous bone, effectively targeting this region for resorption after the systemic release of activated vitamin D metabolites.
authors.affiliation: Bone Research Program, Garvan Institute of Medical Research, St Vincent's Hospital, Sydney, New South Wales, Australia.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Baldock
authors.forename: Gethin P
authors.initials: GP
authors.lastname: Thomas
authors.forename: Jason M
authors.initials: JM
authors.lastname: Hodge
authors.forename: Sara Uk
authors.initials: SU
authors.lastname: Baker
authors.forename: Uwe
authors.initials: U
authors.lastname: Dressel
authors.forename: Peter D
authors.initials: PD
authors.lastname: O'Loughlin
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Nicholson
authors.forename: Kathy H
authors.initials: KH
authors.lastname: Briffa
authors.forename: John A
authors.initials: JA
authors.lastname: Eisman
authors.forename: Edith M
authors.initials: EM
authors.lastname: Gardiner
mesh_terms: D000818:Animals; D016723:Bone Remodeling / Q000187:drug effects*; D001862:Bone Resorption / Q000378:metabolism*; D002136:Calcium, Dietary / Q000008:administration & dosage / Q000494:pharmacology; D018920:Coculture Techniques; D005260:Female; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000378:metabolism*; D053244:Osteoprotegerin / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism; D014807:Vitamin D / Q000494:pharmacology*
chemical_list: D002136:Calcium, Dietary; D053244:Osteoprotegerin; D053245:RANK Ligand; D014807:Vitamin D