RRC ID |
1350
|
著者 |
Fujita T, Azuma Y, Fukuyama R, Hattori Y, Yoshida C, Koida M, Ogita K, Komori T.
|
タイトル |
Runx2 induces osteoblast and chondrocyte differentiation and enhances their migration by coupling with PI3K-Akt signaling.
|
ジャーナル |
J Cell Biol
|
Abstract |
Runx2 and phosphatidylinositol 3-kinase (PI3K)-Akt signaling play important roles in osteoblast and chondrocyte differentiation. We investigated the relationship between Runx2 and PI3K-Akt signaling. Forced expression of Runx2 enhanced osteoblastic differentiation of C3H10T1/2 and MC3T3-E1 cells and enhanced chondrogenic differentiation of ATDC5 cells, whereas these effects were blocked by treatment with IGF-I antibody or LY294002 or adenoviral introduction of dominant-negative (dn)-Akt. Forced expression of Runx2 or dn-Runx2 enhanced or inhibited cell migration, respectively, whereas the enhancement by Runx2 was abolished by treatment with LY294002 or adenoviral introduction of dn-Akt. Runx2 up-regulated PI3K subunits (p85 and p110beta) and Akt, and their expression patterns were similar to that of Runx2 in growth plates. Treatment with LY294002 or introduction of dn-Akt severely diminished DNA binding of Runx2 and Runx2-dependent transcription, whereas forced expression of myrAkt enhanced them. These findings demonstrate that Runx2 and PI3K-Akt signaling are mutually dependent on each other in the regulation of osteoblast and chondrocyte differentiation and their migration.
|
巻・号 |
166(1)
|
ページ |
85-95
|
公開日 |
2004-7-5
|
DOI |
10.1083/jcb.200401138
|
PII |
jcb.200401138
|
PMID |
15226309
|
PMC |
PMC2172136
|
MeSH |
Adenoviridae / genetics
Animals
Blotting, Western
Cell Differentiation
Cell Line
Cell Movement
Cell Nucleus / metabolism
Chondrocytes / cytology*
Chondrocytes / metabolism
Chromatin / metabolism
Chromones / pharmacology
Core Binding Factor Alpha 1 Subunit
DNA / metabolism
Dose-Response Relationship, Drug
Enzyme Inhibitors / pharmacology
Genes, Dominant
Genes, Reporter
Genetic Vectors
Immunohistochemistry
In Situ Hybridization
Mice
Mice, Inbred C3H
Mice, Mutant Strains
Morpholines / pharmacology
Mutation
Neoplasm Proteins / metabolism*
Osteoblasts / cytology*
Osteoblasts / metabolism
Phosphatidylinositol 3-Kinases / metabolism*
Precipitin Tests
Protein Binding
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Transcription Factors / metabolism*
Transfection
Up-Regulation
|
IF |
8.811
|
引用数 |
295
|
WOS 分野
|
CELL BIOLOGY
|
リソース情報 |
ヒト・動物細胞 |
ATDC5(RCB0565)
10T1/2(RCB0247) |