BMP-2-induced Osterix expression is mediated by Dlx5 but is independent of Runx2.
BMP-2 stimulates the expression of three osteogenic master transcription factors: Runx2, Dlx5, and Osterix (Osx). However, the hierarchical regulatory relationships among them are not yet clearly understood. Osx was commonly stimulated in osteogenic and non-osteogenic cells in response to BMP-signaling, as Dlx5 was in our previous report. A cycloheximide experiment indicated that Osx expression by BMP-2 requires new protein synthesis. Even if Osx has been suggested as a downstream target of Runx2, the results of this study indicated that Osx expression was still induced by BMP-2 treatment in Runx2 null cells, but not induced by Runx2 overexpression in myogenic C2C12 cells. Instead, Osx expression by BMP-2 was completely abrogated by the antisense blocking of Dlx5. Depending upon the coincident expression pattern of Osx and Dlx5, and the blocking of Osx expression by the antisense Dlx5, BMP-2-induced Osx expression is mainly mediated not by Runx2, but by Dlx5.
Lee
Mi-Hye
MH
Department of Biochemistry, School of Dentistry, Kyungpook National University, Daegu 700-422, Republic of Korea.
Kwon
Tae-Geon
TG
Park
Hyo-Sang
HS
Wozney
John M
JM
Ryoo
Hyun-Mo
HM
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002454:Cell Differentiation; D002460:Cell Line; D050659:Core Binding Factor Alpha 1 Subunit; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000502:physiology*; D051379:Mice; D008954:Models, Biological; D009363:Neoplasm Proteins; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D016212:Transforming Growth Factor beta
C525719:Bmp2 protein, mouse; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D050659:Core Binding Factor Alpha 1 Subunit; C501120:Dlx5 protein, mouse; D018398:Homeodomain Proteins; D009363:Neoplasm Proteins; D000076182:Sp7 Transcription Factor; C478163:SP7 protein, human; D014157:Transcription Factors; D016212:Transforming Growth Factor beta