Role of MAP Kinases (ERK1andERK2) in Human Periodontal Ligament Cells Proliferation

Objectives: Fibroblast growth factor-2 (FGF-2) is a potent mitogen of human periodontal ligament (HPDL) cells. Although insulin-like growth factor-I (IGF-I) alone is a faint mitogen of HPDL cells , co-stimulation with both FGF-2 and IGF-I clearly enhanced the proliferation of HPDL cells. In this study, we examined the role of the MEK/MAP pathway in HPDL cell proliferation stimulated with FGF-2 and IGF-I. Methods: Using antibodies specific for activated forms of both ERK1 and ERK2, we examined the levels of active MAP kinases (ERK1/2) in HPDL cells treated with FGF-2 and IGF-I. Furthermore, we investigated the effect of U0126, which is a specific inhibitor of MEK/MAP kinase pathway, in the proliferation of HPDL cells by mesuring incorporation of [3H]-thymidine. Results: FGF-2 induced the activation of ERK1/2, and FGF-2 plus IGF-I induced higher level activation than FGF-2 alone did. Those activation of MAP kinases sustained at least up to 24 hours after stimulation by FGF-2 or FGF-2 plus IGF-I. However , IGF-I alone triggered only transient activation of MAP kinases (ERK1/2). And, U0126 clearly inhibited the mitogenic activities of HPDL cells, which were stimulated with FGF-2 or FGF-2 plus IGF-I. Conclusions: These results suggest that MAP kinase pathway played a major role in the proliferation of HPDL cells stimulated by FGF-2 or FGF-2 plus IGF-I.