title: Iloprost up-regulates vascular endothelial growth factor expression in human dental pulp cells in vitro and enhances pulpal blood flow in vivo.
abstract: BACKGROUND
  Prostacyclin (PGI2) is a biomolecule capable of enhancing angiogenesis and cellular proliferation.
  
  
  METHODS
  We investigated the influence of a PGI2 analogue (iloprost) on dental pulp revascularization in vitro and in vivo by using human dental pulp cells (HDPCs) and a rat tooth injury model, respectively. Iloprost stimulated the human dental pulp cell mRNA expression of vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), and platelet-derived growth factor (PDGF) in a significant dose-dependent manner. This mRNA up-regulation was significantly inhibited by pretreatment with a PGI2 receptor antagonist and forskolin (a protein kinase A activator). In contrast, a protein kinase A inhibitor significantly enhanced the iloprost-induced mRNA expression of VEGF, FGF-2, and PDGF. Pretreatment with a fibroblast growth factor receptor inhibitor attenuated the VEGF, FGF-2, and PDGF mRNA expression, indicating opposing regulatory mechanisms.
  
  
  RESULTS
  The effect of iloprost on the dental pulp was investigated in vivo by using a rat molar pulp injury model. The iloprost-treated group exhibited a significant increase in pulpal blood flow at 72 hours compared with control.
  
  
  CONCLUSIONS
  The present study indicates that iloprost may be a candidate agent to promote neovascularization in dental pulp tissue, suggesting the potential clinical use of iloprost in vital pulp therapy.
authors.affiliation: Department of Physiology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand; Mineralized Tissue Research Unit, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand. Electronic address: kandychula@yahoo.com.
authors.forename: Chalida Nakalekha
authors.initials: CN
authors.lastname: Limjeerajarus
authors.affiliation: Mineralized Tissue Research Unit, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand; Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Thanaphum
authors.initials: T
authors.lastname: Osathanon
authors.affiliation: Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Jeeranan
authors.initials: J
authors.lastname: Manokawinchoke
authors.affiliation: Mineralized Tissue Research Unit, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand; Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Prasit
authors.initials: P
authors.lastname: Pavasant
mesh_terms: D000293:Adolescent; D000328:Adult; D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage / Q000494:pharmacology*; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects; D003782:Dental Pulp / Q000098:blood supply / Q000166:cytology / Q000187:drug effects* / Q000293:injuries; D003789:Dental Pulp Exposure / Q000188:drug therapy / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000187:drug effects; D006801:Humans; D016285:Iloprost / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008963:Molar / Q000098:blood supply / Q000293:injuries; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000187:drug effects; D051381:Rats; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors; D012039:Regional Blood Flow / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects*; D055815:Young Adult
chemical_list: D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; D010982:Platelet-Derived Growth Factor; D017468:Receptors, Fibroblast Growth Factor; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D005576:Colforsin; D017868:Cyclic AMP-Dependent Protein Kinases; D016285:Iloprost
keywords: Dental pulp; prostacyclin; pulpal blood flow; vascular endothelial growth factor