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)