Linked Life Data

18814144

Source:http://linkedlifedata.com/resource/pubmed/id/18814144

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2008-11-26
pubmed:abstractText
The expression of receptor activator of nuclear factor-kappaB ligand (RANKL) is regulated by bone-seeking hormones such as PTH and 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3). Runx2, a master gene for osteoblastic differentiation, also modulates osteoclastogenesis by regulating the RANKL gene. To elucidate the mechanism whereby runx2 and 1,25(OH)2D3 regulate RANKL expression, we studied the function of runx2 on the chromatin structure and on the proximal binding sites using osteoblastic cell lines derived from normal (ST2) and runx2-deficient mice (RD-C6). Although the expression of RANKL in the steady-state was higher in RD-C6 than in ST2, 1,25(OH)2D3-treatment of the cells increased it 20-fold in ST2 but only 1.8-fold in RD-C6. Transient transfection studies with proximal RANKL 2kb promoter, runx2 knock-down in ST2, and forced expression of runx2 in RD-C6 all confirmed that runx2 set the steady-state expression of the RANKL gene at a low level, but exerted a positive effect on enhanced transcriptional activity in response to 1,25(OH)2D3. Also, assessment of the acetylation status of the area spanning 40 kb upstream of the basic promoter in ST2 and RD-C6 by ChIP assay revealed that whereas H3 and H4 histone acetylation was detected even in the steady-state in RD-C6, it was detected only with 1,25(OH)2D3 in ST2. In the steady-state, runx2 may suppress RANKL gene by condensing the chromatin structure; however, it exerts a positive effect on 1,25(OH)2D3-induced RANKL transcription when the proximal runx2 sites are accessible. Thus, RANKL expression in stromal/osteoblastic cells is keenly regulated by 1,25(OH)2D3 which transactivates the gene at two different levels
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1097-4644
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
105
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1289-97
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Modulation of mouse RANKL gene expression by Runx2 and vitamin D3.
pubmed:affiliation
Division of Pathology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. kitazawa@med.kobe-u.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't