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Journal of Dental Research
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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

K. Matsushita

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.

REFERENCES

  • Angel P., Karin M. (1991). The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. Biochem Biophys Acta 1072:129-157.[Medline] [Order article via Infotrieve]
  • Barleon B., Sozzani S., Zhou D., Weich HA, Mantovani A., Marine D. (1996). Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1. Blood 87:3336-3343.[Abstract/Free Full Text]
  • Cohen DR, Ferreira PC, Gentz R., Franza BR Jr, Curran T. (1989). The product of a fos-related gene, fra-1, binds cooperatively to the AP-1 site with Jun: transcription factor AP-1 is comprised of multiple protein complexes. Genes Dev 3:173-184.[Abstract/Free Full Text]
  • Chomczynski P., Sacchi N. (1987). Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156-159.[Medline] [Order article via Infotrieve]
  • Detmar M., Yeo KT, Nagy JA, Van de Water L., Brown LF, Berse B., et al. (1995). Keratinocyte-derived vascular permeability factor (vascular endothelial growth factor) is a potent mitogen for dermal microvascular endothelial cells. J Invest Dermatol 105:44-50.[CrossRef][Medline] [Order article via Infotrieve]
  • Dvorak HF, Detmar M., Claffey KP, Nagy JA, van de Water L., Senger DR (1995). Vascular permeability factor/vascular endothelial growth factor: an important mediator of angiogenesis in malignancy and inflammation. Int Arch Allergy Immunol 107:233-235.[CrossRef][Medline] [Order article via Infotrieve]
  • Ferrara N. (1995). The role of vascular endothelial growth factor in pathological angiogenesis. Breast Cancer Res Treat 36:127-137.[CrossRef][Medline] [Order article via Infotrieve]
  • Ferrara N., Henzel WJ (1989). Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun 161:851-858.[CrossRef][Medline] [Order article via Infotrieve]
  • Fujiwara T., Grimm EA, Roth JA ( 1994). Gene therapeutics and gene therapy for cancer. Curr Opin Oncol 6:96-105.[CrossRef][Medline] [Order article via Infotrieve]
  • Goseki M., Oida S., Nifuji A., Sasaki S. (1990). Properties of alkaline phosphatase of the human dental pulp. J Dent Res 69:909-912.
  • Hanatani M., Tanaka Y., Kondo S., Ohmori I., Suzuki H. (1995). Sensitive chemiluminescence enzyme immunoassay for vascular endothelial growth factor/vascular permeability factor in human serum. Biosci Biotechnol Biochem 59:1958-1959.[Medline] [Order article via Infotrieve]
  • Heidenreich 0, Kang SH, Xu X., Nerenberg M. (1995). Application of antisense technology to therapeutics. Mol Med Today 1:128-133.[CrossRef][Medline] [Order article via Infotrieve]
  • Ito A., Hirota S., Mizuno H., Kawasaki Y., Takemura T., Nishiura T., et al. (1995). Expression of vascular permeability factor (VPF/VEGF) messenger RNA by plasma cells: possible involvement in the development of edema in chronic inflammation. Pathol Int 45:715-720.[Medline] [Order article via Infotrieve]
  • Jimi E., Ikebe T., Takahashi N., Hirata M., Suda T., Koga T. ( 1996). Interleukin-la activates an NF-KB-like factor in osteoclast-like cells. J Biol Chem 271:4605-4608.[Abstract/Free Full Text]
  • Jonca F., Ortega N., Gleizes PE, Bertrand N., Plouet J. (1997). Cell release of bioactive fibroblast growth factor 2 by exon 6-encoded sequence of vascular endothelial growth factor. J Biol Chem 272:24203-24209.[Abstract/Free Full Text]
  • Kroll J., Waltenberger J. (1997). The vascular endothelial growth factor receptor KDR activates multiple signal transduction pathways in porcine aortic endothelial cells. J Biol Chem 272:32521-32527.[Abstract/Free Full Text]
  • Lachgar S., Moukadiri H., Jonca F., Charveron M., Bouhaddioui N., Gall Y., et al. (1996). Vascular endothelial growth factor is an autocrine growth factor for hair dermal papilla cells. J Invest Dermatol 106:17-23.[CrossRef][Medline] [Order article via Infotrieve]
  • Li J., Perrella MA, Tsai JC, Yet SF, Hsieh CM, Yoshizumi M., et al. (1995). Induction of vascular endothelial growth factor gene expression by Interleukin-1β in rat aortic smooth muscle cells. JBiol Chem 270:308-312.[Abstract/Free Full Text]
  • Magloire H., Joffre A., Bleicher F. (1996). An in vitro model of human dental pulp repair. J Dent Res 75:1971-1978.
  • Masood R., Cai J., Zheng T., Smith DL, Naidu Y., Gill PS ( 1997). Vascular endothelial growth factor/vascular permeability factor is an autocrine growth factor for AIDS-Kaposi sarcoma. Proc Natl Acad Sci USA 94:979-984.[Abstract/Free Full Text]
  • Matsushita K. Motani R., Sakuta T., Nagaoka S., Matsuyama T., Abeyama K., et al. (1999). Lipopolysaccharide enhances the production of vascular endothelial growth factor by human pulp cells in culture. Infect Immun 67:1633-1639.[Abstract/Free Full Text]
  • Midy V., Plouet J. (1994). Vasculotropin/vascular endothelial growth factor induces differentiation in cultured osteoblasts. Biochem Biophys Res Commun 199:380-386.[CrossRef][Medline] [Order article via Infotrieve]
  • Miller WA, Everett MM, Cramer JF (1976). Growth of bovine pulp cells in monolayer culture. J Endod 2:385-389.[Medline] [Order article via Infotrieve]
  • Nakashima M. (1994). Induction of dentine in amputated pulp of dogs by recombinant human bone morphogenetic proteins-2 and -4 with collagen matrix. Arch Oral Biol 39:1085-1089.[CrossRef][Medline] [Order article via Infotrieve]
  • Nomura M., Yamagishi S., Harada S., Hayashi Y., Yamashita T., Yamashita J., et al. (1995). Possible participation of autocrine and paracrine vascular endothelial growth factors in hypoxia-induced proliferation of endothelial cells and pericytes. J Biol Chem 270:28316-28324.[Abstract/Free Full Text]
  • Owen TA, Holthuis J., Markose E., van Wijnen AJ, Wolfe SA, Grimes SR, et al. (1990). Modifications of protein-DNA interactions in the proximal promoter of a cell-growth-regulated histone gene during onset and progression of osteoblast differentiation. Proc Natl Acad Sci USA 87:5129-5133.[Abstract/Free Full Text]
  • Oyama T., Ran S., Ishida T., Nadaf S., Kerr L., Carbone DP, et al. (1998). Vascular endothelial growth factor affects dendritic cell maturation through the inhibition of nuclear factor-kappa B activation in hemopoietic progenitor cells. J Immunol 160:1224-1232.[Abstract/Free Full Text]
  • Praloran V., Mirshahi S., Favard C., Moukadiri H., Plouet J. (1991). Activite mitogene de la vasculotropine pour les lymphocytes peripheriques humains [Mitogenic activity of vasculotropin for peripheral human lymphocytes]. C R Acad Sci III 313:21-26.[Medline] [Order article via Infotrieve]
  • Puzas JE, Brand JS (1985). Bone cell phosphotyrosine phosphatase: characterization and regulation by calcitropic hormones. Endocrinology 116:2463-2468.[Abstract/Free Full Text]
  • Rauscher FJ 3rd, Cohen DR, Curran T., Bos TJ, Vogt PK, Bohmann D., et al. (1988). Fos-associated protein p39 is the product of the jun proto-oncogene. Science 240:1010-1016.[Abstract/Free Full Text]
  • Roberts-Clark D., Smith AJ (1999). Angiogenic growth factors in dentine matrix (abstract). J Dent Res 78(Spec Iss):143.
  • Rutherford RB, Wahle J., Tucker M., Rueger D., Charette M. (1993). Induction of reparative dentin formation in monkeys by recombinant human osteogenic protein-1. Arch Oral Biol 38:571-576.[CrossRef][Medline] [Order article via Infotrieve]
  • Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF (1983). Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 219:983-985.[Abstract/Free Full Text]
  • Shiba H., Nakamura S., Shirakawa M., Nakanishi K., Okamoto H., Satakeda H., et al. (1995). Effects of basic fibroblast growth factor on proliferation, the expression of osteonectin (SPARC) and alkaline phosphatase, and calcification in cultures of human pulp cells. Dev Biol 170:457-466.[CrossRef][Medline] [Order article via Infotrieve]
  • Shibuya M., Yamaguchi S., Yamane A., Ikeda T., Tojo A., Matsushime H., et al. (1990). Nucleotide sequence and expression of a novel human receptor-type tyrosine kinase gene (flt) closely related to the fms family. Oncogene 5:519-524.[Medline] [Order article via Infotrieve]
  • Takahashi T., Shibuya M. (1997). The 230 kDa mature form of KDR/Flk-1 (VEGF receptor-2) activates the PLC-gamma pathway and partially induces mitotic signals in NIH3T3 fibroblasts. Oncogene 14:2079-2089.[CrossRef][Medline] [Order article via Infotrieve]
  • Terman BI, Carrion ME, Kovacs E., Rasmussen BA, Eddy RL, Shows TB (1991). Identification of a new endothelial cell growth factor receptor tyrosine kinase. Oncogene 6:1677-1683.[Medline] [Order article via Infotrieve]
  • Thomas KA (1996). Vascular endothelial growth factor, a potent and selective angiogenic agent. J Bioi Chem 271:603-606.[Free Full Text]
  • Tziafas D., Alvanou A., Papadimitriou S., Gasic J., Komnenou A. (1998). Effects of recombinant basic growth factor, insulin-like growth factor-II and transforming growth factor-β1 on dog dental pulp cells in vivo. Arch Oral Biol 43:431-444.[Medline] [Order article via Infotrieve]
  • Waltenberger J., Claesson-Welsh L., Siegbahn A., Shibuya M., Heldin CH (1994). Different signal transduction properties of KDR and Fltl, two receptors for vascular endothelial growth factor. J Biol Chem 269:26988-26995.[Abstract/Free Full Text]
  • Yamaguchi N., Yamashita Y., Ikeda D., Koga T. ( 1996). Actinobacillus actinomycetemcomitans serotype b-specific polysaccharide antigen stimulates production of chemotactic factors and inflammatory cytokines by human monocytes. Infect Immun 64:2563-2570.[Abstract]
  • Yamane A., Seetharam L., Yamaguchi S., Gotoh N., Takahashi T., Neufeld G., et al. (1994). A new communication system between hepatocytes and sinusoidal endothelial cells in liver through vascular endothelial growth factor and Fit tyrosine kinase receptor family (Flt-1 and KDR/Flk-1). Oncogene 9:2683-2690.[Medline] [Order article via Infotrieve]

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