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??1 or FGF?2 significantly decreased EMD?induced VEGF production, whereas the addition of exogenous TGF??1 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…
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