title: Isoprenoid geranylgeraniol: the influence on cell characteristics of endothelial progenitor cells after bisphosphonate therapy in vitro.
abstract: OBJECTIVE
  Geranylgeraniol (GGOH) has been reported as a potential treatment option for bisphosphonate-associated osteonecrosis of the jaws (BP-ONJ). The aim of this study was to analyze the effects of GGOH on endothelial progenitor cells (EPC) after bisphosphonate treatment in vitro.
  
  
  METHODS
  EPC were incubated with different nitrogen (N-BPs: ibandronate, pamidronate, zoledronate) and a non-nitrogen-containing bisphosphonates (NN-BP: clodronate) with and without GGOH. Cell viability was measured by MTT and PrestoBlue assay. Migration ability was analyzed with a Boyden and Scratch assay. Apoptosis rates were determined by colony-forming, Tunel and ToxiLight assays.
  
  
  RESULTS
  Negative effects of N-BPs on EPC were shown in all tests without GGOH. The substitution of GGOH demonstrated significantly increased cell viability (MTT: p each N-BP ≤0.004; PrestoBlue: p each N-BP <0.001) and migration ability (Boyden: p each N-BP <0.001; Scratch: p each N-BP <0.001). Concerning the apoptosis rates, increased EPC colony densities (p each N-BP ≤0.009), decreased numbers of apoptotic cells in the Tunel assay (p each N-BP <0.001), and a decreased adenylate kinase release in the ToxiLight assay (p each N-BP ≤0.03) were observed. For the clodronate-treated cells, no significant differences could be detected with or without GGOH in any assay (p each N-BP/NN-BP >0.05).
  
  
  CONCLUSIONS
  GGOH cell treatment reversed the negative effects of bisphosphonates on EPC.
  
  
  CONCLUSIONS
  These findings support the hypothesis that systemic or local GGOH treatment might lead to new therapeutic strategies for BP-ONJ.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University Medical Center Mainz, Augustusplatz 2, 55131, Mainz, Germany.
authors.forename: A M
authors.initials: AM
authors.lastname: Pabst
authors.forename: M
authors.initials: M
authors.lastname: Krüger
authors.forename: T
authors.initials: T
authors.lastname: Ziebart
authors.forename: C
authors.initials: C
authors.lastname: Jacobs
authors.forename: C
authors.initials: C
authors.lastname: Walter
mesh_terms: D004164:Diphosphonates / Q000494:pharmacology*; D004224:Diterpenes / Q000494:pharmacology*; D066026:Endothelial Progenitor Cells / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques
chemical_list: D004164:Diphosphonates; D004224:Diterpenes; C017338:geranylgeraniol