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Vitamin D action and regulation of bone remodeling : suppression of osteoclastogenesis by the mature osteoblast

Baldock, Paul A.; Thomas, Gethin P; Hodge, Jason M; Baker, Sara Uk LU ; Dressel, Uwe; O'Loughlin, Peter D; Nicholson, Geoffrey C.; Briffa, Kathy H; Eisman, John A and Gardiner, Edith M. (2006) In Journal of Bone and Mineral Research 21(10). p.26-1618
Abstract

UNLABELLED: 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.

INTRODUCTION: 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... (More)

UNLABELLED: 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.

INTRODUCTION: 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.

MATERIALS AND 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.

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publishing date
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Contribution to journal
publication status
published
keywords
Animals, Bone Remodeling, Bone Resorption, Calcium, Dietary, Coculture Techniques, Female, Humans, Mice, Mice, Transgenic, Osteoblasts, Osteoprotegerin, RANK Ligand, Vitamin D, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
in
Journal of Bone and Mineral Research
volume
21
issue
10
pages
9 pages
publisher
AMBMR
external identifiers
  • scopus:33749237867
ISSN
0884-0431
DOI
10.1359/jbmr.060714
language
English
LU publication?
no
id
079174b5-dc20-445b-a179-fb3c5b425744
date added to LUP
2017-03-09 15:02:24
date last changed
2018-07-01 04:43:57
@article{079174b5-dc20-445b-a179-fb3c5b425744,
  abstract     = {<p>UNLABELLED: 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.</p><p>INTRODUCTION: 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.</p><p>MATERIALS AND 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.</p><p>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.</p><p>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.</p>},
  author       = {Baldock, Paul A. and Thomas, Gethin P and Hodge, Jason M and Baker, Sara Uk and Dressel, Uwe and O'Loughlin, Peter D and Nicholson, Geoffrey C. and Briffa, Kathy H and Eisman, John A and Gardiner, Edith M.},
  issn         = {0884-0431},
  keyword      = {Animals,Bone Remodeling,Bone Resorption,Calcium, Dietary,Coculture Techniques,Female,Humans,Mice,Mice, Transgenic,Osteoblasts,Osteoprotegerin,RANK Ligand,Vitamin D,Comparative Study,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {10},
  pages        = {26--1618},
  publisher    = {AMBMR},
  series       = {Journal of Bone and Mineral Research},
  title        = {Vitamin D action and regulation of bone remodeling : suppression of osteoclastogenesis by the mature osteoblast},
  url          = {http://dx.doi.org/10.1359/jbmr.060714},
  volume       = {21},
  year         = {2006},
}