TY - JOUR
T1 - PDGF up-regulates CSF-1 gene transcription in ameloblast-like cells
AU - Wittrant, Y.
AU - Bhandari, B. Sriniketan
AU - Abboud, H.
AU - Benson, N.
AU - Woodruff, K.
AU - MacDougall, M.
AU - Abboud-Werner, S.
PY - 2008/1
Y1 - 2008/1
N2 - Macrophage colony-stimulating factor (CSF-I) is a key regulatory cytokine for amelogenesis, and ameloblasts synthesize CSF-I. We hypothesized that PDGF stimulates DNA synthesis and regulates CSF-I in these cells. We determined the effect of PDGF on CSF-I 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-I mRNA and protein in MEOE-3M. Cells transfected with CSF1 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 PDGFBB is a mitogen for MEOE-3M and increases CSF-I 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.
AB - Macrophage colony-stimulating factor (CSF-I) is a key regulatory cytokine for amelogenesis, and ameloblasts synthesize CSF-I. We hypothesized that PDGF stimulates DNA synthesis and regulates CSF-I in these cells. We determined the effect of PDGF on CSF-I 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-I mRNA and protein in MEOE-3M. Cells transfected with CSF1 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 PDGFBB is a mitogen for MEOE-3M and increases CSF-I 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.
KW - Ameloblasts
KW - Gene transcription
KW - Macrophage colony-stimulating factor
KW - Platelet-derived growth factor
KW - Transcription factors
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U2 - 10.1177/154405910808700105
DO - 10.1177/154405910808700105
M3 - Article
C2 - 18096890
AN - SCOPUS:38149032632
VL - 87
SP - 33
EP - 38
JO - Journal of Dental Research
JF - Journal of Dental Research
SN - 0022-0345
IS - 1
ER -