| RRC ID |
6560
|
| 著者 |
Itoh S, Kanno S, Gai Z, Suemoto H, Kawakatsu M, Tanishima H, Morimoto Y, Nishioka K, Hatamura I, Yoshida M, Muragaki Y.
|
| タイトル |
Trps1 plays a pivotal role downstream of Gdf5 signaling in promoting chondrogenesis and apoptosis of ATDC5 cells.
|
| ジャーナル |
Genes Cells
|
| Abstract |
Tricho-rhino-phalangeal syndrome (TRPS) is an autosomal dominant skeletal disorder caused by mutations of TRPS1. Based on the similar expression patterns of Trps1 and Gdf5, we hypothesized a possible functional interaction between these two molecules. Using a chondrogenic cell line (ATDC5), we investigated the association of Gdf5-mediated signaling pathways with Trps1 and the phenotypic changes of ATDC5 cells due to over-expression or suppression of Trps1. Treatment of cells with Gdf5 enhanced Trps1 protein levels and phosphorylation of p38 mitogen-activated protein kinase (MAPK) in a dose-dependent manner. Nuclear translocation of Trps1 was also induced by Gdf5. These effects were blocked by a dominant negative form of activin-linked kinase 6 (dn-Alk6) and by SB203580, an inhibitor of the p38 MAPK pathway. Conversely, Gdf5 expression was suppressed by the over-expression of Trps1. Trps1-overexpressing ATDC5 (O/E) cells differentiated into chondrocytes more quickly than mock-infected control cells, whereas cells transfected with dn-Alk6 showed slower differentiation. On the other hand, O/E cells showed an increase of apoptosis along with the up-regulation of cleaved caspase 3 and down-regulation of Bcl-2, whereas dn-Alk6 cells showed suppression of apoptosis. In conclusion, Trps1 acts downstream of the Gdf5 signaling pathway and promotes the differentiation and apoptosis of ATDC5 cells.
|
| 巻・号 |
13(4)
|
| ページ |
355-63
|
| 公開日 |
2008-4-1
|
| DOI |
10.1111/j.1365-2443.2008.01170.x
|
| PII |
GTC1170
|
| PMID |
18363966
|
| MeSH |
Animals
Apoptosis / physiology*
Base Sequence
Bone Diseases, Developmental / genetics
Bone Morphogenetic Protein Receptors, Type I / genetics
Bone Morphogenetic Protein Receptors, Type I / metabolism
Bone Morphogenetic Proteins / metabolism*
Cell Line
Chondrogenesis / physiology*
Craniofacial Abnormalities / genetics
DNA Primers / genetics
Feedback
GATA Transcription Factors / genetics
GATA Transcription Factors / metabolism*
Gene Expression
Growth Differentiation Factor 5
Mice
Phenotype
Repressor Proteins
Signal Transduction
Transfection
p38 Mitogen-Activated Protein Kinases / metabolism
|
| IF |
1.655
|
| 引用数 |
25
|
|
WOS 分野
|
GENETICS & HEREDITY
CELL BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
ATDC5(RCB0565) |
