title: Cooperative effects of FGF-2 and VEGF-A in periodontal ligament cells.
abstract: We previously demonstrated that topical application of fibroblast growth factor (FGF)-2 enhanced periodontal tissue regeneration. Although angiogenesis is a crucial event for tissue regeneration, the mechanism(s) by which topically applied FGF-2 induces angiogenesis in periodontal tissues has not been fully clarified. In this study, we investigated whether FGF-2 could induce vascular endothelial growth factor (VEGF)-A expression in periodontal ligament (PDL) cells and whether cell-to-cell interactions between PDL cells and endothelial cells could stimulate angiogenesis. FGF-2 induced VEGF-A secretion from MPDL22 cells (mouse periodontal ligament cell line) in a dose-dependent manner. Transwell and wound-healing assays revealed that co-stimulation with FGF-2 plus VEGF-A synergistically stimulated the migration of MPDL22 cells. Interestingly, co-culture of MPDL22 cells with bEnd5 cells (mouse endothelial cell line) also stimulated VEGF-A production from MPDL22 cells and tube formation by bEnd5 cells. Furthermore, time-lapse analysis revealed that MPDL22 cells migrated close to the tube-forming bEnd5 cells, mimicking pericytes. Thus, FGF-2 induces VEGF-A expression in PDL cells and induces angiogenesis in combination with VEGF-A. Cell-to-cell interactions with PDL cells also facilitate angiogenesis.
authors.affiliation: Division of Oral Biology and Disease Control, Department of Periodontology, Osaka University, Suita, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yanagita
authors.forename: Y
authors.initials: Y
authors.lastname: Kojima
authors.forename: M
authors.initials: M
authors.lastname: Kubota
authors.forename: K
authors.initials: K
authors.lastname: Mori
authors.forename: M
authors.initials: M
authors.lastname: Yamashita
authors.forename: S
authors.initials: S
authors.lastname: Yamada
authors.forename: M
authors.initials: M
authors.lastname: Kitamura
authors.forename: S
authors.initials: S
authors.lastname: Murakami
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000187:drug effects; D018929:Cell Culture Techniques; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D018920:Coculture Techniques; D004396:Coloring Agents; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D042783:Endothelial Cells / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D018613:Microscopy, Confocal; D008870:Microtubules / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects; D020286:Pericytes / Q000187:drug effects; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects*; D011994:Recombinant Proteins; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: D004396:Coloring Agents; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D016222:Fibroblast Growth Factor 2
keywords: cell communication; cell migration; endothelial cells; growth factors; pericytes; tissue regeneration