title: In vitro inhibition of HUVECs by low dose methotrexate - insights into oral adverse events.
abstract: BACKGROUND
  With socio-economic changes, dentists and maxillofacial surgeons are more and more faced with medically compromised patients. Especially, the admission of antirheumatic drugs has increased remarkably. So dentists and maxillofacial surgeons should be aware of related adverse reactions that affect the craniofacial region. To identify possible cellular effects of disease modifying antirheumatic drugs (DMARDs) we investigated the influence of methotrexate (MTX) on human umbilical vein endothelial cells (HUVECs).
  
  
  METHODS
  HUVECs were incubated with various concentrations of MTX, corresponding to serum concentrations found in rheumatoid arthritis (RA) patients. The effect of MTX on cell proliferation, differentiation as well as mitochondrial activity was measured by use of immunostaining, cell counting and 3-(4, 5-dimethylthiazol-2-yl)- 2, 5-diphenyltetrazolium bromide (MTT) assay.
  
  
  RESULTS
  All samples incubated with MTX (1-1000 nM) showed significantly decreased cell viability when compared to controls. Cells were less proliferating, but did not lose their ability to synthesize endothelial proteins. A slight dose dependency of inhibiting effects was demonstrated. The observed differences between control and sample groups were rising with longer duration.
  
  
  CONCLUSIONS
  Because of the crucial role of endothelial cells and their precursor cells in wound healing, a negative influence of MTX on oral health has to be supposed, correlating to clinical observations of adverse reactions in the oral cavity, such as ulcerative or erosive lesions.
authors.affiliation: Department of Cranio-Maxillofacial Surgery, University Hospital of Muenster, Research Group Vascular Biology of Oral Structures (VABOS), Waldeyerstr,30, Muenster 48149, Germany. tobias.annussek@ukmuenster.de.
authors.forename: Tobias
authors.initials: T
authors.lastname: Annussek
authors.forename: Thomas
authors.initials: T
authors.lastname: Szuwart
authors.forename: Johannes
authors.initials: J
authors.lastname: Kleinheinz
authors.forename: Cathrin
authors.initials: C
authors.lastname: Koiky
authors.forename: Kai
authors.initials: K
authors.lastname: Wermker
mesh_terms: D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects*; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects*; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
chemical_list: D018501:Antirheumatic Agents; D008727:Methotrexate