title: Bisphosphonate effects on the behaviour of oral epithelial cells and oral fibroblasts.
abstract: OBJECTIVE
  Bisphosphonates (BPs) like Zometa (ZA) are widely used to treat complications of bony metastases in cancer patients. A serious adverse event occurs in 1-12% of patients on BP therapy, osteonecrosis of the jaw (BPONJ). BPONJ develops after oral trauma and is manifested by poor wound healing and soft-tissue breakdown followed by exposure and necrosis of intra-oral bone. Currently, there is no effective clinical treatment for BPONJ.
  
  
  METHODS
  We evaluated the effect of ZA on the proliferation, apoptosis and migratory capacity of the cell lines CRL-7408, an oral fibroblast culture and OKF/6, an oral epithelial cell line.
  
  
  RESULTS
  In both oral epithelium and fibroblasts, ZA exposure inhibited proliferation and elevated apoptosis; however oral fibroblasts were differentially influenced versus oral epithelial cells. In oral fibroblasts, ZA treatment significantly inhibited motility. Further, quantitative real-time PCR demonstrated that ZA treatment of oral fibroblasts inhibits expression of both the COL1A1 and COL1A2 chains of type-I collagen, consistent with a loss of collagen immunofluorescent staining.
  
  
  CONCLUSIONS
  These data support a model wherein ZA treatment impedes oral wound healing by blocking the growth and migratory capacity of oral fibroblasts as well as downregulating the transcription of type-I collagen, functions necessary to deposit the granulation tissue needed for re-epithelization. Therefore, BP released from bone following tooth extraction may delay wound healing of the oral mucosal barrier and contribute to BPONJ pathogenesis.
authors.affiliation: Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, Columbia, MO 65212, United States.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Ravosa
authors.forename: Jie
authors.initials: J
authors.lastname: Ning
authors.forename: Yueying
authors.initials: Y
authors.lastname: Liu
authors.forename: M Sharon
authors.initials: MS
authors.lastname: Stack
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000187:drug effects; D004164:Diphosphonates / Q000009:adverse effects*; D015536:Down-Regulation; D004847:Epithelial Cells / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects*; D007571:Jaw Diseases / Q000139:chemically induced; D009061:Mouth Mucosa / Q000166:cytology* / Q000187:drug effects*; D010020:Osteonecrosis / Q000139:chemically induced; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013194:Staining and Labeling; D014081:Tooth Extraction; D014945:Wound Healing / Q000187:drug effects*; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D003094:Collagen