title: The influence of bisphosphonates on human osteoblast migration and integrin aVb3/tenascin C gene expression in vitro.
abstract: BACKGROUND
  Bisphosphonates are therapeutics of bone diseases, such as Paget's disease, multiple myeloma or osteoclastic metastases. As a severe side effect the bisphosphonate induced osteonecrosis of the jaw (BONJ) often requires surgical treatment and is accompanied with a disturbed wound healing.Therefore, the influence on adhesion and migration of human osteoblasts (hOB) after bisphosphonate therapy has been investigated by morphologic as well as gene expression methods.
  
  
  METHODS
  By a scratch wound experiment, which measures the reduction of defined cell layer gap, the morphology and migration ability of hOB was evaluated. A test group of hOB, which was stimulated by zoledronate 5 × 10(-5)M, and a control group of unstimulated hOB were applied. Furthermore the gene expression of integrin aVb3 and tenascin C was quantified by Real-Time rtPCR at 5 data points over an experimental period of 14 days. The bisphosphonates zoledronate, ibandronate and clodronate have been compared with an unstimulated hOB control.
  
  
  RESULTS
  After initially identical migration and adhesion characteristics, zoledronate inhibited hOB migration after 50 h of stimulation. The integrinavb3 and tenascin C gene expression was effected by bisphosphonates in a cell line dependent manner with decreased, respectively inconsistent gene expression levels over time. The non-nitrogen containing bisphosphonates clodronate led to decreased gene expression levels.
  
  
  CONCLUSIONS
  Bisphosphonates seem to inhibit hOB adhesion and migration. The integrin aVb3 and tenascin C gene expression seem to be dependent on the cell line. BONJ could be enhanced by an inhibition of osteoblast adhesion and migration. The gene expression results, however, suggest a cell line dependent effect of bisphosphonates, which could explain the interindividual differences of BONJ incidences.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University medical centre of Johannes Gutenberg University Mainz, Augustusplatz 2, 55131 Mainz, Germany.
authors.forename: Felix P
authors.initials: FP
authors.lastname: Koch
authors.forename: Annette
authors.initials: A
authors.lastname: Wunsch
authors.forename: Christina
authors.initials: C
authors.lastname: Merkel
authors.forename: Thomas
authors.initials: T
authors.lastname: Ziebart
authors.forename: Andreas
authors.initials: A
authors.lastname: Pabst
authors.forename: Sareh Said
authors.initials: SS
authors.lastname: Yekta
authors.forename: Marco
authors.initials: M
authors.lastname: Blessmann
authors.forename: Ralf
authors.initials: R
authors.lastname: Smeets
mesh_terms: D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics; D004164:Diphosphonates / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D039302:Integrin alphaVbeta3 / Q000235:genetics; D010006:Osteoblasts / Q000187:drug effects*; D019063:Tenascin / Q000235:genetics; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D039302:Integrin alphaVbeta3; D019063:Tenascin; D000077211:Zoledronic Acid