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Enamel matrix derivative induces production of vascular endothelial cell growth factor in human gingival fibroblasts
Author(s) -
Sakoda Kenji,
Nakajima Yumiko,
Noguchi Kazuyuki
Publication year - 2012
Publication title -
european journal of oral sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.802
H-Index - 93
eISSN - 1600-0722
pISSN - 0909-8836
DOI - 10.1111/j.1600-0722.2012.00999.x
Subject(s) - enamel matrix derivative , vascular endothelial growth factor , angiogenesis , fibroblast growth factor , mapk/erk pathway , chemistry , extracellular matrix , microbiology and biotechnology , basic fibroblast growth factor , transforming growth factor , kinase , p38 mitogen activated protein kinases , growth factor , fibroblast , vascular endothelial growth factor a , protein kinase a , cancer research , biology , biochemistry , vegf receptors , receptor , regeneration (biology) , in vitro
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‐ β 1 ( TGF ‐ β 1), or fibroblast growth factor 2 ( FGF ‐2), with or without antibodies to TGF ‐ β 1 or FGF ‐2. The levels of VEGF in the culture media were measured using an ELISA . We examined the effects of SB 203580 [a p38 mitogen‐activated protein kinase ( MAPK ) inhibitor], U 0126 [an extracellular signal‐regulated kinase ( ERK ) inhibitor], SP 600125 [a c‐ J un N ‐terminal kinase ( JNK ) inhibitor], and LY 294002 [a phosphatidylinositol 3‐kinase ( PI 3 K )/ A kt 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 ‐ β 1 or FGF ‐2 significantly decreased EMD ‐induced VEGF production, whereas the addition of exogenous TGF ‐ β 1 and FGF ‐2 stimulated VEGF production. Enamel matrix derivative‐induced VEGF production was significantly attenuated by SB 203580, U 0126, and LY 294002. Our results suggest that EMD stimulates VEGF production partially via TGF ‐ β 1 and FGF ‐2 in human gingival fibroblasts and that EMD ‐induced VEGF production is regulated by ERK , p38 MAPK , and PI 3 K / A kt 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.