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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

Department of Operative Dentistry and Endodontology, Kagoshima University Dental School, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan, macken{at}dentb.hal.kagoshima-u.ac.jp

R. Motani

Department of Operative Dentistry and Endodontology, Kagoshima University Dental School, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan

T. Sakutal

Department of Operative Dentistry and Endodontology, Kagoshima University Dental School, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan

N. Yamaguchi

Department of Preventive Dentistry, Kyushu University Faculty of Dentistry, Fukuoka 812-8582, Japan

T. Koga

Department of Preventive Dentistry, Kyushu University Faculty of Dentistry, Fukuoka 812-8582, Japan

K. Matsuo

Department of Bioscience Research, Tsukuba Research Laboratory, Toagosei Co., Ltd., Ibaragi 300-33, Japan

S. Nagaoka

Department of Operative Dentistry and Endodontology, Kagoshima University Dental School, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan

K. Abeyama

Department of Clinical Laboratory Medicine, Kagoshima University Medical School, Kagoshima 890-8544, Japan

I. Maruyama

Department of Clinical Laboratory Medicine, Kagoshima University Medical School, Kagoshima 890-8544, Japan

M. Torii

Department of Operative Dentistry and Endodontology, Kagoshima University Dental School, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan

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, fms-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 I (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.

Key Words: vascular endothelial growth factor • human pulp cells • autocrine • AP-1.

Journal of Dental Research, Vol. 79, No. 8, 1596-1603 (2000)
DOI: 10.1177/00220345000790081201


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