title: Hinokitiol increases the angiogenic potential of dental pulp cells through ERK and p38MAPK activation and hypoxia-inducible factor-1α (HIF-1α) upregulation.
abstract: Hinokitiol, a natural iron-chelating agent, is known to have diverse biological and pharmacological activities in various cell types. However, the effect of hinokitiol on dental pulp cells has not yet been reported. In this study, hinokitiol increases hypoxia-inducible factor-1α (HIF-1α) protein levels and vascular endothelial growth factor (VEGF) secretion in human dental pulp cells. The extracellular-signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) pathways are involved in hinokitiol-induced HIF-1α protein expression in dental pulp cells. Conditioned media from hinokitiol-treated pulp cells enhances angiogenesis in vitro and in vivo. Overall, these results show that hinokitiol promotes ERK and p38MAPK activation and HIF-1α-induced VEGF production, thus increasing the angiogenic potential of dental pulp cells.
authors.affiliation: Department of Oral Physiology, School of Dentistry, Pusan National University, Yangsan 626-870, South Korea.
authors.forename: Mi-Kyoung
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Department of Oral Physiology, School of Dentistry, Pusan National University, Yangsan 626-870, South Korea; Department of Dental Pharmacology, School of Dentistry, Pusan National University, Yangsan 626-870, South Korea.
authors.forename: Hyun-Joo
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Pusan National University, Yangsan 626-870, South Korea.
authors.forename: Yong-Deok
authors.initials: YD
authors.lastname: Kim
authors.affiliation: Department of Oral Pathology, School of Dentistry, Pusan National University, Yangsan 626-870, South Korea.
authors.forename: Mi Heon
authors.initials: MH
authors.lastname: Ryu
authors.affiliation: Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Takata
authors.affiliation: Department of Dental Pharmacology, School of Dentistry, Pusan National University, Yangsan 626-870, South Korea.
authors.forename: Soo-Kyung
authors.initials: SK
authors.lastname: Bae
authors.affiliation: Department of Oral Physiology, School of Dentistry, Pusan National University, Yangsan 626-870, South Korea. Electronic address: mkbae@pusan.ac.kr.
authors.forename: Moon-Kyoung
authors.initials: MK
authors.lastname: Bae
mesh_terms: D015153:Blotting, Western; D003782:Dental Pulp / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D017930:Genes, Reporter; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007150:Immunohistochemistry; D007502:Iron Chelating Agents / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D039821:Monoterpenes / Q000494:pharmacology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014334:Tropolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007502:Iron Chelating Agents; D039821:Monoterpenes; D014334:Tropolone; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; C009479:beta-thujaplicin
keywords: Angiogenesis; Dental pulp cells; ERK; HIF-1α; Hinokitiol; Hypoxia-inducible factor-1 alpha; VEGF; extracellular-signal-regulated kinase; hypoxia-inducible factor-1 alpha; p38 mitogen-activated protein kinase; p38MAPK; vascular endothelial growth factor