Increased formation and decreased resorption of bone in mice with elevated vitamin D receptor in mature cells of the osteoblastic lineage

Gardiner, Edith M., Baldock, Paul A., Thomas, Gethin P., Sims, Natalie A., Henderson, N. Kathryn, Hollis, Bruce, White, Christopher P., Sunn, Kathryn L., Morrison, Nigel A., Walsh, William R. and Eisman, John A. (2000) Increased formation and decreased resorption of bone in mice with elevated vitamin D receptor in mature cells of the osteoblastic lineage. FASEB Journal, 14 13: 1908-1916. doi:10.1096/fj.99-1075com


Author Gardiner, Edith M.
Baldock, Paul A.
Thomas, Gethin P.
Sims, Natalie A.
Henderson, N. Kathryn
Hollis, Bruce
White, Christopher P.
Sunn, Kathryn L.
Morrison, Nigel A.
Walsh, William R.
Eisman, John A.
Title Increased formation and decreased resorption of bone in mice with elevated vitamin D receptor in mature cells of the osteoblastic lineage
Journal name FASEB Journal   Check publisher's open access policy
ISSN 0892-6638
1530-6860
Publication date 2000-10
Sub-type Article (original research)
DOI 10.1096/fj.99-1075com
Volume 14
Issue 13
Start page 1908
End page 1916
Total pages 9
Place of publication Bethesda, MD, United States
Publisher Federation of American Societies for Experimental Biology
Language eng
Abstract The microarchitecture of bone is regulated by complex interactions between the bone-forming and resorbing cells, and several compounds regulate both actions. For example, vitamin D, which is required for bone mineralization, also stimulates bone resorption. Transgenic mice overexpressing the vitamin D receptor solely in mature cells of the osteoblastic bone-forming lineage were generated to test the potential therapeutic value of shifting the balance of vitamin D activity in favor of bone formation. Cortical bone was 5% wider and 15% stronger in these mice due to a doubling of periosteal mineral apposition rate without altered body weight or calcium homeostatic hormone levels. A 20% increase in trabecular bone volume in transgenic vertebrae was also observed, unexpectedly associated with a 30% reduction in resorption surface rather than greater bone formation. These findings indicate anabolic vitamin D activity in bone and identify a previously unknown pathway from mature osteoblastic cells to inhibit osteoclastic bone resorption, counterbalancing the known stimulatory action through immature osteoblastic cells. A therapeutic approach that both stimulates cortical anabolic and inhibits trabecular resorptive pathways would be ideal for treatment of osteoporosis and other osteopenic disorders.
Keyword Osteoclast
Osteocyte
Periosteum
Uncoupling
Turnover
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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Created: Mon, 21 Mar 2011, 12:33:04 EST