Runx2 regulates FGF2-induced Bmp2 expression during cranial bone development.
Calvarial bone is formed by the intramembranous bone-forming process, which involves many signaling molecules. The constitutive activation of the fibroblast growth factor (FGF) signaling pathway accelerates osteoblast differentiation and results in premature cranial suture closure. Bone morphogenetic protein (BMP) signaling pathways, which involve the downstream transcription factors Dlx5 and Msx2, are also involved in the bone-forming processes. However, the relationships between these two main signaling cascades are still unclear. We found that FGF2 treatment of developing bone fronts stimulated Bmp2 gene expression but that BMP2 treatment could not induce Fgf2 expression. Moreover, the disruption of the Runx2 gene completely eliminated the expression of Bmp2 and its downstream genes Dlx5 and Msx2 in the developing primordium of bone, while the expression of Fgf2 was maintained. In addition, cultured Runx2-/- cells expressed very low baseline levels of Bmp2 that were up-regulated by transfection with a Runx2-expressing plasmid. These levels in turn were markedly elevated by FGF2 treatment. FGF2 treatment also strongly enhanced the Bmp2 expression in MC3T3-E1 cells, whose endogenous Runx2 gene is intact and which express Bmp2 at low baseline levels as well. These results indicate that Runx2 is an important mediator of the expression of Bmp2 in response to FGF stimulation in cranial bone development.
Choi
Kang-Young
KY
Department of Biochemistry, School of Dentistry and Skeletal Diseases Genome Research Center, Kyungpook National University, 101 Dong In-dong, Jung-gu, Daegu, 700-422, Korea.
Kim
Hyun-Jung
HJ
Lee
Mi-Hye
MH
Kwon
Tae-Geon
TG
Nah
Hyun-Duck
HD
Furuichi
Tatsuya
T
Komori
Toshihisa
T
Nam
Soon-Hyeun
SH
Kim
Young-Jin
YJ
Kim
Hyun-Jung
HJ
Ryoo
Hyun-Mo
HM
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D050659:Core Binding Factor Alpha 1 Subunit; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D009363:Neoplasm Proteins / Q000378:metabolism*; D012886:Skull / Q000196:embryology*; D014157:Transcription Factors / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D050659:Core Binding Factor Alpha 1 Subunit; D009363:Neoplasm Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2