Runx2 induces osteoblast and chondrocyte differentiation and enhances their migration by coupling with PI3K-Akt signaling.
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.
Fujita
Takashi
T
Department of Pharmacology, Setsunan University, Hirakata, Japan.
Azuma
Yasutaka
Y
Fukuyama
Ryo
R
Hattori
Yuji
Y
Yoshida
Carolina
C
Koida
Masao
M
Ogita
Kiyokazu
K
Komori
Toshihisa
T
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002460:Cell Line; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D050659:Core Binding Factor Alpha 1 Subunit; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005799:Genes, Dominant; D017930:Genes, Reporter; D005822:Genetic Vectors; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D009025:Morpholines / Q000494:pharmacology; D009154:Mutation; D009363:Neoplasm Proteins / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation
D002843:Chromatin; D002867:Chromones; D050659:Core Binding Factor Alpha 1 Subunit; D004791:Enzyme Inhibitors; D009025:Morpholines; D009363:Neoplasm Proteins; D014157:Transcription Factors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D004247:DNA; D019869:Phosphatidylinositol 3-Kinases