title: Enamel matrix derivative induces production of vascular endothelial cell growth factor in human gingival fibroblasts.
abstract: Enamel matrix derivative (EMD) may enhance periodontal wound healing by inducing angiogenesis. We sought to investigate the effect and the mechanism of action of EMD on vascular endothelial growth factor (VEGF) production by human gingival fibroblasts. Cells were stimulated with EMD, transforming growth factor-β1 (TGF-β1), or fibroblast growth factor 2 (FGF-2), with or without antibodies to TGF-β1 or FGF-2. The levels of VEGF in the culture media were measured using an ELISA. We examined the effects of SB203580 [a p38 mitogen-activated protein kinase (MAPK) inhibitor], U0126 [an extracellular signal-regulated kinase (ERK) inhibitor], SP600125 [a c-Jun N-terminal kinase (JNK) inhibitor], and LY294002 [a phosphatidylinositol 3-kinase (PI3K)/Akt inhibitor] on EMD-induced VEGF production. Enamel matrix derivative stimulated the production of VEGF in a dose- and time-dependent manner. Treatment of human gingival fibroblasts with antibodies to TGF-β1 or FGF-2 significantly decreased EMD-induced VEGF production, whereas the addition of exogenous TGF-β1 and FGF-2 stimulated VEGF production. Enamel matrix derivative-induced VEGF production was significantly attenuated by SB203580, U0126, and LY294002. Our results suggest that EMD stimulates VEGF production partially via TGF-β1 and FGF-2 in human gingival fibroblasts and that EMD-induced VEGF production is regulated by ERK, p38 MAPK, and PI3K/Akt pathways. Enamel matrix derivative-induced production of VEGF by human gingival fibroblasts may be involved in the enhancement of periodontal wound healing by inducing angiogenesis.
authors.affiliation: Department of Periodontology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakoda
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Nakajima
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Noguchi
mesh_terms: D000704:Analysis of Variance; D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003746:Dental Enamel Proteins / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D020869:Gene Expression Profiling; D005881:Gingiva / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D043925:Angiogenesis Inducing Agents; D003746:Dental Enamel Proteins; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2