TNF-α enhances MMP-2 production in deciduous dental pulp fibroblasts

Inflammation in dental pulp tissue is associated with tissue degradation, and matrix metalloproteinases (MMPs) are believed to participate in this destruction. Elevated levels of some MMPs have been reported in inflamed pulp and periapical lesions. Moreover, in inflamed pulp, many kinds of inflammatory cytokines such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α, are released from inflammatory cells like macrophages, lymphocytes and neutrophils. In the present study, we examined whether TNF-α affected the production of MMP-2 in deciduous dental pulp fibroblasts and its signaling pathways utilizing gelatin zymography and western blotting analysis. TNF-α increased the expression of MMP-2 in a dose-dependent manner in deciduous dental pulp fibroblasts. LY294002 and Wortmannin, which are PI3-K (phosphoinositide 3-kinase) inhibitors, inhibited the MMP-2 production induced by TNF-α in deciduous dental pulp fibroblasts. Moreover, in deciduous dental pulp fibroblasts cultured with TNF-α, AKT (protein kinase B) was phosphorylated in a time-dependent manner with the maximum phosphorylation at 30 min, and LY294002 and Wortmannin abolished this phosphorylation of AKT in TNF-α-stimulated deciduous dental pulp fibroblasts. These results suggest that TNF-α may enhance pulp tissue destruction during pulp inflammation in part by regulating MMP-2, and that the AKT pathway is involved in MMP-2 production in deciduous dental pulp fibroblasts.