The suppressive effect of myeloid Elf-1-like factor (MEF) in osteogenic differentiation.
Myeloid Elf-1 like factor (MEF) is a member of the Ets transcription factor family. Ets family proteins control the expression of genes that are critical for biological processes such as proliferation, differentiation, and cell death. Some of Ets factors are also known to regulate bone development. In this study, we investigated the role of MEF in osteoblast differentiation. MEF expression was highest early in the differentiation of MC3T3-E1 osteoblasts and was reduced by treatment with BMP-2. The expression of MEF suppressed the alkaline phosphatase activity and expression induced by BMP-2 stimulation and mediated by Runx2. The expression of MEF also reduces osteocalcin mRNA levels, and mineralization in MC3T3-E1 cells. We found that the MEF-mediated suppression of osteogenic differentiation was critically related to Runx2 regulation. The MEF and Runx2 proteins physically interact to form a complex, and this interaction interferes with Runx2 binding to the cis-acting element OSE2 derived from the osteocalcin promoter. Co-transfection of MEF inhibited the 6xOSE2-luciferase reporter activity induced by Runx2. In addition, MEF stimulated the transcription of a negative mediator Msx2, and a transcriptional repressor, Mab21L1, and suppressed the transcription of a positive mediator, Dlx5 in osteoblast differentiation. MEF overexpression stimulated C2C12 cell proliferation. Together, our findings suggest that MEF promotes cell proliferation and functions as a negative regulator of osteogenic differentiation by directly interacting with Runx2 and suppressing its transcriptional activity.
Kim
Youn-Jeong
YJ
Department of Biochemistry and BK 21 Program, Kyungpook National University, Daegu, Korea.
Kim
Byung-Gyu
BG
Lee
Seung-Jin
SJ
Lee
Ho-Kyung
HK
Lee
Sang-Han
SH
Ryoo
Hyun-Mo
HM
Cho
Je-Yoel
JY
D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D002113:Calcification, Physiologic / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
C525718:BMP2 protein, human; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D050659:Core Binding Factor Alpha 1 Subunit; D004268:DNA-Binding Proteins; C491779:Elf4 protein, mouse; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D015675:Osteocalcin; D008156:Luciferases; D000469:Alkaline Phosphatase