The Role of Vascular Endothelial Growth Factor in Human Dental Pulp Cells: Induction of Chemotaxis, Proliferation, and Differentiation and Activation of the AP-1-dependent Signaling Pathway

Abstract

Vascular endothelial growth factor (VEGF) is a potent mitogen in endothelial cells, but little is known about its activity in other cell types. To clarify the role of VEGF in human dental pulp cells and pulp tissue, we investigated the effects of VEGF on the chemotaxis, proliferation, and differentiation of human dental pulp cells. VEGF induced a strong chemotactic response in human dental pulp cells in a dose-dependent manner. VEGF also marginally enhanced the proliferation of human dental pulp cells and induced an increase in alkaline phosphatase in human dental pulp cells. However, these effects of VEGF were not observed in reference to human skin fibroblasts. Analyses by the reverse-transcription/polymerase-chain-reaction method and flow cytometry showed that the mRNAs of two VEGF receptors, fins-like tyrosine kinase and kinase insert domain-containing receptor, were expressed in human dental pulp cells, whereas only fms-like tyrosine kinase mRNA was expressed in human skin fibroblasts. VEGF induced the activation of activator protein 1 (AP-1) and c-fos mRNA expression in human dental pulp cells. The AP-1 inhibitor curcumin strongly inhibited VEGF-induced alkaline phosphatase production in human dental pulp cells. In addition, VEGF antisense oligonucleotide suppressed the production of VEGF and alkaline phosphatase in human dental pulp cells. These results suggest that VEGF produced by human dental pulp cells acts directly upon human dental pulp cells in an autocrine manner, and may promote the chemotaxis, proliferation, and/or differentiation of human dental pulp cells via the utilization of kinase insert domain-containing receptor and in part through AP-1 by increasing c-fos.

Neuropeptide Release from Dental Pulp Cells by RgpB via Proteinase-Activated Receptor-2 Signaling

“…7C). This binding activity was induced by the same concentration of nuclear protein extracted from recombinant human vascular endothelial growth factor-treated cells as shown previously (31). The AP-1 DNA-binding complex was completely displaced by the excess addition of an unlebeled AP-1 oligonucleotide probe but not with the mutated AP-1 element in the competition assay.…”

“…Human pulp cells (HPCs) were prepared as described previously (31). Briefly, normal human dental pulp tissue was obtained from extracted first premolars and was cultured in ␣-MEM (ICN Biomedicals) supplemented with 10% FBS.…”

Analysis of FOS, BTG2, and NR4A in the function of renal medullary hypertension

“…FOS interacts with C-jun to upregulate the transcription of a diverse range of genes involved in biological processes from proliferation and differentiation to defense against pathogen invasion and cell damage (Bossis et al, 2005). FOS is a potent mitogen in endothelial cells that, and it also marginally enhances the proliferation of and increases alkaline phosphatase in human dental pulp cells (Matsushita et al, 2000). However, these effects are not observed in human skin fibroblasts.…”

Odontogenic differentiation of vascular endothelial growth factor-transfected human dental pulp stem cells in vitro

“…Vascular endothelial growth factor (VEGF) is an important cytokine that can promote the osteogenic differentiation of cells. A previous study demonstrated that recombinant human VEGF improved the cell proliferation and alkaline phosphatase (ALP) expression of dental pulp cells (6). VEGF culture medium also promoted the osteogenic differentiation capacity of MC3T3 stem cells by increasing the expression of ALP and osteocalcin (OCN) in vitro (7).…”