| RRC ID |
61403
|
| 著者 |
Lee MH, Kim YJ, Kim HJ, Park HD, Kang AR, Kyung HM, Sung JH, Wozney JM, Kim HJ, Ryoo HM.
|
| タイトル |
BMP-2-induced Runx2 expression is mediated by Dlx5, and TGF-beta 1 opposes the BMP-2-induced osteoblast differentiation by suppression of Dlx5 expression.
|
| ジャーナル |
J Biol Chem
|
| Abstract |
Intramuscular injection of BMP-2 induces ectopic bone formation in vivo. Similarly, BMP-2 treatment blocks myogenic differentiation and induces osteoblastic transdifferentiation of premyoblastic C2C12 cells. Previous reports suggested that BMP-2-stimulated Runx2 expression could play a pivotal role in transdifferentiation. However, increased Runx2 expression by TGF-beta 1 did not support osteoblast differentiation in vitro. These results indicate that the induction of Runx2 is not sufficient to explain the BMP-induced transdifferentiation. We found that Dlx5 is specifically expressed in osteogenic cells, and is specifically induced by BMP-2 or -4 signaling but not by other osteotrophic signals or other TGF-beta superfamily members. Cycloheximide treatment indicated that Dlx5 was immediately induced by BMP signaling, while Runx2 required de novo protein synthesis. In addition, blocking or overexpressing each transcription factor indicated that Dlx5 is an indispensable mediator of BMP-2-induced Runx2 expression but is not involved in TGF-beta 1-induced Runx2 expression. Moreover, TGF-beta 1 opposed BMP-2-induced osteogenic transdifferentiation through Dlx5 suppression by de novo induction of AP-1. Taken together, these results indicate that Dlx5 is an indispensable regulator of BMP-2-induced osteoblast differentiation as well as the counteraction point of the opposing TGF-beta 1 action.
|
| 巻・号 |
278(36)
|
| ページ |
34387-94
|
| 公開日 |
2003-9-5
|
| DOI |
10.1074/jbc.M211386200
|
| PII |
S0021-9258(20)83755-7
|
| PMID |
12815054
|
| MeSH |
Alkaline Phosphatase / metabolism
Animals
Blotting, Northern
Blotting, Southern
Blotting, Western
Bone Morphogenetic Protein 2
Bone Morphogenetic Proteins / metabolism*
Cell Differentiation
Cell Line
Core Binding Factor Alpha 1 Subunit
Cycloheximide / pharmacology
Dose-Response Relationship, Drug
Down-Regulation
Homeodomain Proteins / metabolism*
Mice
Neoplasm Proteins*
Osteoblasts / cytology
Osteoblasts / metabolism
Plasmids / metabolism
Protein Synthesis Inhibitors / pharmacology
RNA / metabolism
Rats
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Transcription Factors / biosynthesis*
Transcription Factors / metabolism*
Transfection
Transforming Growth Factor beta / metabolism*
Transforming Growth Factor beta1
Tumor Cells, Cultured
|
| IF |
4.238
|
| リソース情報 |
| ヒト・動物細胞 |
ATDC5(RCB0565) |
