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J Dent Res 87(1):33-38, 2008
© 2008 International and American Associations for Dental Research

RESEARCH REPORT
Biological

PDGF Up-regulates CSF-1 Gene Transcription in Ameloblast-like Cells

Y. Wittrant1, B. Sriniketan Bhandari2, H. Abboud2, N. Benson3, K. Woodruff1, M. MacDougall4, and S. Abboud-Werner1,*

1 Departments of Pathology and
2 Medicine, and
3 Dental School, University of Texas Health Science Center, 7703 Floyd Curl Drive, and South Texas Veterans Health Care System, Audie Murphy Division, San Antonio, TX 78229, USA; and
4 School of Dentistry, University of Alabama at Birmingham, Birmingham, AL 35294, USA

* corresponding author, AbboudWerner{at}uthscsa.edu

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.

KEY WORDS: macrophage colony-stimulating factor • platelet-derived growth factor • ameloblasts • gene transcription • transcription factors






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