title: 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.
authors.affiliation: Department of Operative Dentistry and Endodontology, Kagoshima University Dental School, Japan. macken@dentb.hal.kagoshima-u.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Matsushita
authors.forename: R
authors.initials: R
authors.lastname: Motani
authors.forename: T
authors.initials: T
authors.lastname: Sakuta
authors.forename: N
authors.initials: N
authors.lastname: Yamaguchi
authors.forename: T
authors.initials: T
authors.lastname: Koga
authors.forename: K
authors.initials: K
authors.lastname: Matsuo
authors.forename: S
authors.initials: S
authors.lastname: Nagaoka
authors.forename: K
authors.initials: K
authors.lastname: Abeyama
authors.forename: I
authors.initials: I
authors.lastname: Maruyama
authors.forename: M
authors.initials: M
authors.lastname: Torii
mesh_terms: D000469:Alkaline Phosphatase / Q000096:biosynthesis; D019898:Autocrine Communication; D001667:Binding, Competitive; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D003782:Dental Pulp / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D008222:Lymphokines / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis; D017978:Receptors, Growth Factor / Q000096:biosynthesis; D011975:Receptors, Mitogen / Q000096:biosynthesis; D040262:Receptors, Vascular Endothelial Growth Factor; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000819:agonists*; D014158:Transcription, Genetic / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D008222:Lymphokines; D016376:Oligonucleotides, Antisense; D016760:Proto-Oncogene Proteins c-fos; D017978:Receptors, Growth Factor; D011975:Receptors, Mitogen; D011994:Recombinant Proteins; D018808:Transcription Factor AP-1; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D000469:Alkaline Phosphatase