| RRC ID |
42193
|
| Author |
Ogasawara T, Kawaguchi H, Jinno S, Hoshi K, Itaka K, Takato T, Nakamura K, Okayama H.
|
| Title |
Bone morphogenetic protein 2-induced osteoblast differentiation requires Smad-mediated down-regulation of Cdk6.
|
| Journal |
Mol Cell Biol
|
| Abstract |
Because a temporal arrest in the G(1) phase of the cell cycle is thought to be a prerequisite for cell differentiation, we investigated cell cycle factors that critically influence the differentiation of mouse osteoblastic MC3T3-E1 cells induced by bone morphogenetic protein 2 (BMP-2), a potent inducer of osteoblast differentiation. Of the G(1) cell cycle factors examined, the expression of cyclin-dependent kinase 6 (Cdk6) was found to be strongly down-regulated by BMP-2/Smads signaling, mainly via transcriptional repression. The enforced expression of Cdk6 blocked BMP-2-induced osteoblast differentiation to various degrees, depending on the level of its overexpression. However, neither BMP-2 treatment nor Cdk6 overexpression significantly affected cell proliferation, suggesting that the inhibitory effect of Cdk6 on cell differentiation was exerted by a mechanism that is largely independent of its cell cycle regulation. These results indicate that Cdk6 is a critical regulator of BMP-2-induced osteoblast differentiation and that its Smads-mediated down-regulation is essential for efficient osteoblast differentiation.
|
| Volume |
24(15)
|
| Pages |
6560-8
|
| Published |
2004-8-1
|
| DOI |
10.1128/MCB.24.15.6560-6568.2004
|
| PII |
24/15/6560
|
| PMID |
15254224
|
| PMC |
PMC444857
|
| MeSH |
Animals
Blotting, Western
Bone Morphogenetic Protein 2
Bone Morphogenetic Proteins / metabolism*
Bromodeoxyuridine / pharmacology
Cell Cycle
Cell Differentiation
Cell Line
Chromatin / metabolism
Cyclin-Dependent Kinase 6
Cyclin-Dependent Kinases / biosynthesis*
DNA-Binding Proteins / metabolism*
Down-Regulation*
Flow Cytometry
G1 Phase
Mice
Models, Biological
Osteoblasts / metabolism*
Precipitin Tests
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Smad Proteins
Time Factors
Trans-Activators / metabolism*
Transcription, Genetic
Transforming Growth Factor beta*
|
| IF |
3.611
|
| Times Cited |
89
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
| Resource |
| Human and Animal Cells |
MC3T3-E1(RCB1126) |
