| RRC ID |
18669
|
| 著者 |
Hu R, Liu W, Li H, Yang L, Chen C, Xia ZY, Guo LJ, Xie H, Zhou HD, Wu XP, Luo XH.
|
| タイトル |
A Runx2/miR-3960/miR-2861 regulatory feedback loop during mouse osteoblast differentiation.
|
| ジャーナル |
J Biol Chem
|
| Abstract |
Our recent study showed that miR-2861 promotes osteoblast differentiation by targeting histone deacetylase 5, resulting in increased runt-related transcription factor 2 (Runx2) protein production. Here we identified another new microRNA (miRNA) (miR-3960) that played a regulatory role in osteoblast differentiation through a regulatory feedback loop with miR-2861. miR-3960 and miR-2861 were found clustered at the same loci. miR-3960 was transcribed during bone morphogenic protein 2 (BMP2)-induced osteogenesis of ST2 stromal cells. Overexpression of miR-3960 promoted BMP2-induced osteoblastogenesis. However, the inhibition of miR-3960 expression attenuated the osteoblastogenesis. Homeobox A2 (Hoxa2), a repressor of Runx2 expression, was confirmed to be a target of miR-3960. Electrophoretic mobility shift assay and chromatin immunoprecipitation experiments confirmed that Runx2 bound to the promoter of the miR-3960/miR-2861 cluster. Furthermore, overexpression of Runx2 induced miR-3960/miR-2861 transcription, and block of Runx2 expression attenuated BMP2-induced miR-3960/miR-2861 transcription. Here we report that miR-3960 and miR-2861, transcribed together from the same miRNA polycistron, both function in osteoblast differentiation through a novel Runx2/miR-3960/miR-2861 regulatory feedback loop. Our findings provide new insights into the roles of miRNAs in osteoblast differentiation.
|
| 巻・号 |
286(14)
|
| ページ |
12328-39
|
| 公開日 |
2011-4-8
|
| DOI |
10.1074/jbc.M110.176099
|
| PII |
S0021-9258(20)51612-8
|
| PMID |
21324897
|
| PMC |
PMC3069436
|
| MeSH |
Animals
Animals, Newborn
Blotting, Northern
Blotting, Western
Cell Differentiation / genetics
Cell Differentiation / physiology
Cells, Cultured
Chromatin Immunoprecipitation
Computational Biology
Core Binding Factor Alpha 1 Subunit / genetics
Core Binding Factor Alpha 1 Subunit / metabolism*
Electrophoretic Mobility Shift Assay
Homeodomain Proteins / genetics
Homeodomain Proteins / metabolism*
Mice
Mice, Inbred C57BL
MicroRNAs / genetics
MicroRNAs / physiology*
Osteoblasts / cytology*
Osteoblasts / metabolism
RNA, Small Interfering / genetics
Reverse Transcriptase Polymerase Chain Reaction
|
| IF |
4.238
|
| 引用数 |
166
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
ST2(RCB0224) |
