PDGF up-regulates CSF-1 gene transcription in ameloblast-like cells.
Macrophage colony-stimulating factor (CSF-1) is a key regulatory cytokine for amelogenesis, and ameloblasts synthesize CSF-1. We hypothesized that PDGF stimulates DNA synthesis and regulates CSF-1 in these cells. We determined the effect of PDGF on CSF-1 expression using MEOE-3M ameloblasts as a model. By RT-PCR, MEOE-3M expressed PDGFRs and PDGF A- and B-chain mRNAs. PDGF-BB increased DNA synthesis and up-regulated CSF-1 mRNA and protein in MEOE-3M. Cells transfected with CSF-1 promoter deletion constructs were analyzed. A PDGF-responsive region between -1.7 and -0.795 kb, containing a consensus Pea3 binding motif, was identified. Electrophoretic mobility shift assay (EMSA) showed that PDGF-BB stimulated protein binding to this motif that was inhibited in the presence of anti-Pea3 antibody. Analysis of these data provides the first evidence that PDGF-BB is a mitogen for MEOE-3M and increases CSF-1 protein levels, predominantly by transcription. Elucidation of the cellular pathways that control CSF-1 expression may provide novel strategies for the regulation of enamel matrix formation.
Wittrant
Y
Y
Department of Pathology, University of Texas Health Science Center, San Antonio, TX 78229, USA.
Bhandari
B Sriniketan
BS
Abboud
H
H
Benson
N
N
Woodruff
K
K
MacDougall
M
M
Abboud-Werner
S
S
D000565:Ameloblasts / Q000378:metabolism*; D020816:Amino Acid Motifs / Q000235:genetics; D000818:Animals; D000077214:Becaplermin; D002478:Cells, Cultured; D017124:Conserved Sequence / Q000235:genetics; D004247:DNA / Q000096:biosynthesis; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008934:Mitogens / Q000494:pharmacology; D023421:Models, Animal; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics; D017384:Sequence Deletion / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics*; D014162:Transfection; D015854:Up-Regulation
D008934:Mitogens; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D014157:Transcription Factors; C075278:platelet-derived growth factor A; C065788:transcription factor PEA3; D000077214:Becaplermin; D016173:Macrophage Colony-Stimulating Factor; D004247:DNA; D017479:Receptors, Platelet-Derived Growth Factor