Enamel matrix derivative stimulates human gingival fibroblast proliferation via ERK.
Emdogain, a formulation of Enamel Matrix Proteins, is used clinically for periodontal regeneration to stimulate PDL (periodontal ligament), cementum, and bone formation. Its effects on gingival fibroblasts and tissue have not been thoroughly studied. Therefore, we investigated the mechanisms by which Emdogain affects the cell cycle of human gingival fibroblasts. Without serum, Emdogain (50 microg/mL) induced human gingival fibroblast entry into the S phase and DNA synthesis, but not completion of the cell cycle. With low serum concentrations (0.2-0.5%), Emdogain synergistically induced completion of the cell cycle, resulting in increased cell numbers. The mitogenic response to Emdogain depended on Extracellular Regulated Kinase (ERK) activation, which occurred in two waves, peaking after 15 min and 4 to 6 hrs, since it was abolished by U0126, a specific MAPK inhibitor. Inhibition of the second wave was sufficient to abrogate mitogenesis. This study characterized the mitogenic effect of Emdogain on primary human gingival fibroblasts, its cooperation with serum growth factors, and the key mediatory role of the ERK cascade.
Zeldich
E
E
Department of Oral Biology, Tel-Aviv University, Israel.
Koren
R
R
Nemcovsky
C
C
Weinreb
M
M
D001769:Blood; D002070:Butadienes / Q000494:pharmacology; D002452:Cell Count; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D003470:Culture Media; D016895:Culture Media, Serum-Free; D004247:DNA / Q000096:biosynthesis; D003746:Dental Enamel Proteins / Q000494:pharmacology*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects*; D005881:Gingiva / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D008938:Mitosis / Q000187:drug effects; D009570:Nitriles / Q000494:pharmacology; D016196:S Phase; D013997:Time Factors
D002070:Butadienes; D003470:Culture Media; D016895:Culture Media, Serum-Free; D003746:Dental Enamel Proteins; D004791:Enzyme Inhibitors; D009570:Nitriles; C113580:U 0126; C109069:enamel matrix proteins; D003094:Collagen; D004247:DNA; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases