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)