RRC ID |
6533
|
著者 |
Suemoto H, Muragaki Y, Nishioka K, Sato M, Ooshima A, Itoh S, Hatamura I, Ozaki M, Braun A, Gustafsson E, Fässler R.
|
タイトル |
Trps1 regulates proliferation and apoptosis of chondrocytes through Stat3 signaling.
|
ジャーナル |
Dev Biol
|
Abstract |
Mutations in the TRPS1 gene lead to the tricho-rhino-phalangeal syndrome, which is characterized by skeletal defects and abnormal hair development. The TRPS1 gene encodes an atypical member of the GATA-type family of transcription factors. Here we show that mice with a disrupted Trps1 gene develop a chondrodysplasia characterized by diminished chondrocyte proliferation and decreased apoptosis in growth plates. Our analyses revealed that Trps1 is a repressor of Stat3 expression, which in turn controls chondrocyte proliferation and survival by regulating the expression of cyclin D1 and Bcl2. Our conclusion is supported (i) by siRNA-mediated depletion of Stat3 in Trps1-deficient chondrocytes, which normalized the expression of cyclin D1 and Bcl2, (ii) by overexpression of Trps1 in ATDC5 chondrocytes, which diminished Stat3 levels and increased proliferation and apoptosis, and (iii) by mutational analysis of the GATA-binding sites in the Stat3 gene, which revealed that their integrity is critical for the direct association with Trps1 and for Trps1-mediated repression of Stat3. Altogether our findings identify Trps1 as a novel regulator of chondrocytes proliferation and survival through the control of Stat3 expression.
|
巻・号 |
312(2)
|
ページ |
572-81
|
公開日 |
2007-12-15
|
DOI |
10.1016/j.ydbio.2007.10.001
|
PII |
S0012-1606(07)01412-1
|
PMID |
17997399
|
MeSH |
Animals
Blastocyst / metabolism
Cell Differentiation
Cell Proliferation
Chondrocytes / cytology
Chondrocytes / metabolism*
Female
GATA Transcription Factors / genetics
GATA Transcription Factors / metabolism
GATA Transcription Factors / physiology*
Mice
Mice, Inbred C57BL
Mice, Transgenic
Promoter Regions, Genetic
Repressor Proteins / genetics
Repressor Proteins / metabolism
Repressor Proteins / physiology*
STAT3 Transcription Factor / genetics
STAT3 Transcription Factor / metabolism*
Signal Transduction*
|
IF |
2.896
|
引用数 |
75
|
WOS 分野
|
DEVELOPMENTAL BIOLOGY
|
リソース情報 |
ヒト・動物細胞 |
ATDC5(RCB0565) |