Document Detail

Stimulation of osteoclast formation by 1,25-dihydroxyvitamin D requires its binding to vitamin D receptor (VDR) in osteoblastic cells: studies using VDR knockout mice.
MedLine Citation:
PMID:  9927335     Owner:  NLM     Status:  MEDLINE    
Previous studies have shown that 1,25-dihydroxyvitamin D [1,25(OH)2D] plays important roles in the formation of osteoclasts through its actions on osteoblastic cells. We have generated mice lacking vitamin D receptor (VDR) by gene targeting (VDR-/-). These mice had tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts, and exhibited similar levels of parameters for bone resorption to those in wild type mice. The present studies were undertaken to clarify whether effects of 1,25(OH)2D on osteoclast formation require VDR in osteoblasts, and to examine mechanisms of the formation of osteoclasts without VDR-mediated actions using VDR-/- mice. When wild-type calvarial osteoblasts and spleen cells were co-cultured with 1,25(OH)2D, TRAP-positive osteoclasts were formed regardless of the genotypes of spleen cells. In contrast, when osteoblasts from VDR-/- mice were co-cultured, no osteoclasts could be formed even with wild-type spleen cells. Parathyroid hormone and interleukin-1alpha stimulated osteoclast formation by co-cultures from VDR-/- mice, and the generated osteoclasts showed resorbing activity. These results demonstrate that VDR-mediated actions of 1,25(OH)2D in osteoblasts are essential for osteoclast formation by 1,25(OH)2D, and that functionally intact osteoclasts can be formed without 1,25(OH)2D actions under stimulations by other agents. It is suggested that osteoclastic bone resorption can be maintained without 1,25(OH)2D actions by other stimulatory agents.
S Takeda; T Yoshizawa; Y Nagai; H Yamato; S Fukumoto; K Sekine; S Kato; T Matsumoto; T Fujita
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Endocrinology     Volume:  140     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  1999 Feb 
Date Detail:
Created Date:  1999-02-23     Completed Date:  1999-02-23     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1005-8     Citation Subset:  AIM; IM    
Fourth Dept. of Internal Medicine, University of Tokyo, Japan.
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MeSH Terms
Acid Phosphatase / metabolism
Cell Differentiation / drug effects,  physiology
Coculture Techniques
Isoenzymes / metabolism
Mice, Knockout / genetics
Osteoblasts / cytology
Osteoclasts / cytology,  physiology*
Receptors, Calcitriol / genetics,  metabolism*
Spleen / cytology
Vitamin D / analogs & derivatives*,  metabolism,  pharmacology
Reg. No./Substance:
0/Isoenzymes; 0/Receptors, Calcitriol; 1406-16-2/Vitamin D; 66772-14-3/1,25-dihydroxyvitamin D; EC 3.1.3.-/tartrate-resistant acid phosphatase; EC Phosphatase

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