Document Detail

Decreased AP-1 activity and interleukin-11 expression by bone marrow stromal cells may be associated with impaired bone formation in aged mice.
MedLine Citation:
PMID:  12929935     Owner:  NLM     Status:  MEDLINE    
Expression of an osteogenic cytokine, IL-11, is decreased in SAMP6. We show here that IL-11 transcription largely depends on AP-1 transcription factors, activities of which are decreased in SAMP6 as well as aged ICR mice. Therefore, diminished AP-1 activity and the resultant decline in IL-11 expression may play a role in impaired bone formation in the aged. INTRODUCTION: Evidence suggests that impaired osteoblastogenesis contributes to aging-associated osteopenia. The P6 strain of senescence-accelerated mice (SAM) is an animal model of senile osteoporosis, which exhibits low bone mass caused by impaired bone formation. Bone marrow stromal cells from SAMP6 show decreased osteoblastogenesis and increased adipogenesis. We previously demonstrated that these abnormalities of SAMP6 stromal cells may be attributed to decreased expression of interleukin (IL)-11. METHODS: In this study, we attempted to determine the molecular mechanism of decreased IL-11 expression by SAMP6 stromal cells by cloning and analyzing the mouse IL-11 gene promoter. RESULTS AND CONCLUSIONS: We found that two tandem activating protein-1 (AP-1) sites that reside immediately upstream of TATA box play critical roles in IL-11 gene transcription. Gel shift analysis showed that binding activity to the IL-11 AP-1 sites was reduced in SAMP6 stromal cell nuclear extracts. Among multiple components of AP-1 transcription factors, Jun D binding was particularly decreased. Furthermore, decreased Jun D binding and IL-11 expression by stromal cells was also observed in aged mice of the ICR strain. Therefore, decreased AP-1 activity and a resultant decline in IL-11 expression by bone marrow stromal cells may play a role in impaired bone formation in the aged.
Emiko Tohjima; Daisuke Inoue; Nobuchika Yamamoto; Shinsuke Kido; Yuji Ito; Shuji Kato; Yasuhiro Takeuchi; Seiji Fukumoto; Toshio Matsumoto
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research     Volume:  18     ISSN:  0884-0431     ISO Abbreviation:  J. Bone Miner. Res.     Publication Date:  2003 Aug 
Date Detail:
Created Date:  2003-08-21     Completed Date:  2004-04-01     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8610640     Medline TA:  J Bone Miner Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1461-70     Citation Subset:  IM    
Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine, Tokushima, Japan.
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MeSH Terms
5' Untranslated Regions / genetics
Aging / genetics,  physiology*
Base Sequence
Bone Marrow Cells / metabolism*
Cell Line
Cloning, Molecular
Gene Expression Regulation
Interleukin-11 / genetics*,  metabolism*
Mice, Inbred ICR
Molecular Sequence Data
Osteogenesis / physiology*
Promoter Regions, Genetic / genetics
Protein Binding
Proto-Oncogene Proteins c-jun / metabolism
RNA, Messenger / genetics,  metabolism
Sequence Alignment
Stromal Cells / metabolism*
Transcription Factor AP-1 / metabolism*
Reg. No./Substance:
0/5' Untranslated Regions; 0/Interleukin-11; 0/Proto-Oncogene Proteins c-jun; 0/RNA, Messenger; 0/Transcription Factor AP-1

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