RRC ID |
43877
|
著者 |
Suzuki D, Yamada A, Aizawa R, Funato S, Matsumoto T, Suzuki W, Takami M, Miyamoto Y, Suzawa T, Yamamoto M, Baba K, Kamijo R.
|
タイトル |
BMP2 differentially regulates the expression of Gremlin1 and Gremlin2, the negative regulators of BMP function, during osteoblast differentiation.
|
ジャーナル |
Calcif Tissue Int
|
Abstract |
Bone morphogenetic proteins (BMPs) control the expressions of many genes involved in bone formation. On the basis of our hypothesis that BMP2 stimulation-regulated gene expression plays a critical role in osteoblast differentiation, we performed genome-wide screening of messenger RNA from BMP2-treated and -untreated C2C12 cells using a DNA microarray technique. We found that the expressions of Gremlin1 and Gremlin2, which are known BMP antagonists, were bidirectionally regulated by BMP2. Gremlin1 was down-regulated by BMP2, while Gremlin2 was up-regulated in both time- and dose-dependent manners. Ablation of Gremlin1 or Gremlin2 enhanced osteoblast differentiation induced by BMP2. On the other hand, treatment with recombinant Gremlin1 inhibited BMP2-induced osteoblast differentiation. Furthermore, treatment with Smad4 siRNA and the p38 MAPK inhibitor SB203580 suppressed BMP2-induced Gremlin2 gene expression. The differential regulation of Gremlin1 and Gremlin2 gene expressions by BMP2 may explain the critical function of these genes during osteoblast differentiation.
|
巻・号 |
91(1)
|
ページ |
88-96
|
公開日 |
2012-7-1
|
DOI |
10.1007/s00223-012-9614-5
|
PMID |
22644325
|
MeSH |
Animals
Bone Morphogenetic Protein 2 / antagonists & inhibitors
Bone Morphogenetic Protein 2 / genetics
Bone Morphogenetic Protein 2 / metabolism*
Cell Differentiation*
Cells, Cultured
Cytokines
Gene Expression Regulation
Mice
Osteoblasts / cytology*
Osteoblasts / metabolism
Proteins / genetics*
Proteins / metabolism
RNA, Small Interfering / metabolism
Signal Transduction
Smad4 Protein / genetics
Smad4 Protein / metabolism
|
IF |
3.423
|
引用数 |
19
|
WOS 分野
|
ENDOCRINOLOGY & METABOLISM
|
リソース情報 |
ヒト・動物細胞 |
C2C12(RCB0987) |