論文 - 詳細
| RRC ID | 62171 |
|---|---|
| 著者 | Tohjima E, Inoue D, Yamamoto N, Kido S, Ito Y, Kato S, Takeuchi Y, Fukumoto S, Matsumoto T. |
| タイトル | Decreased AP-1 activity and interleukin-11 expression by bone marrow stromal cells may be associated with impaired bone formation in aged mice. |
| ジャーナル | J Bone Miner Res |
| Abstract |
UNLABELLED: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. |
| 巻・号 | 18(8) |
| ページ | 1461-70 |
| 公開日 | 2003-8-1 |
| DOI | 10.1359/jbmr.2003.18.8.1461 |
| PMID | 12929935 |
| MeSH | 5' Untranslated Regions / genetics Aging / genetics Aging / physiology* Animals Base Sequence Bone Marrow Cells / metabolism* Cell Line Cloning, Molecular Gene Expression Regulation Humans Interleukin-11 / genetics* Interleukin-11 / metabolism* Mice Mice, Inbred ICR Molecular Sequence Data Osteogenesis / physiology* Promoter Regions, Genetic / genetics Protein Binding Proto-Oncogene Proteins c-jun / metabolism RNA, Messenger / genetics RNA, Messenger / metabolism Sequence Alignment Stromal Cells / metabolism* Transcription Factor AP-1 / metabolism* |
| IF | 5.854 |
| リソース情報 | |
| ヒト・動物細胞 | MC3T3-E1(RCB1126) |