title: MAPK signaling is required for LPS-induced VEGF in pulp stem cells.
abstract: Caries-induced pulpitis is typically accompanied by an increase in dental pulp microvascular density. However, the mechanisms by which dental pulp cells recognize lipopolysaccharides (LPSs) remain unclear. We hypothesized that Porphyromonas endodontalis and Escherichia coli LPSs induce vascular endothelial growth factor (VEGF) expression in dental pulp stem cells (DPSC) and human dental pulp fibroblasts (HDPF) through mitogen-activated protein kinase (MAPK) signaling. ELISA, semi-quantitative RT-PCR, immunofluorescence, and Western blots were used. Here, we observed that LPSs induced VEGF expression in DPSC and HDPF cells, and both cell types express Toll-like receptor 4 (TLR- 4). Notably, LPS-induced VEGF is associated with phosphorylation of protein kinase C (PKC zeta) and extracellular signal-regulator kinase (ERK1/2) and is dependent upon MAPK activation. Analysis of these data, collectively, unveils a signaling pathway responsible for synthesis of VEGF by pulp cells and suggests a novel therapeutic target for the management of vascular responses in teeth with pulpitis.
authors.affiliation: Department of Cariology, Restorative Sciences, and Endodontics, University of Michigan School of Dentistry, 1011 N. University, Rm. 1376 D, Ann Arbor, Michigan 48109-1078, USA. tbotero@umich.edu
authors.forename: T M
authors.initials: TM
authors.lastname: Botero
authors.forename: J S
authors.initials: JS
authors.lastname: Son
authors.forename: D
authors.initials: D
authors.lastname: Vodopyanov
authors.forename: M
authors.initials: M
authors.lastname: Hasegawa
authors.forename: C E
authors.initials: CE
authors.lastname: Shelburne
authors.forename: J E
authors.initials: JE
authors.lastname: Nör
mesh_terms: D000704:Analysis of Variance; D003782:Dental Pulp / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D004926:Escherichia coli / Q000276:immunology / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D045202:Porphyromonas endodontalis / Q000276:immunology / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D015290:Second Messenger Systems / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D018709:Statistics, Nonparametric; D013234:Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D000099221:Protein Kinase C zeta
chemical_list: D008070:Lipopolysaccharides; D020928:Mitogen-Activated Protein Kinases; D011493:Protein Kinase C; D051197:Toll-Like Receptor 4; D042461:Vascular Endothelial Growth Factor A; D000099221:Protein Kinase C zeta; C495345:TLR4 protein, human