title: PRGF exerts a cytoprotective role in zoledronic acid-treated oral cells.
abstract: OBJECTIVE
  Bisphosphonates-related osteonecrosis of the jaw (BRONJ) is a common problem in patients undergoing long-term administration of highly potent nitrogen-containing bisphosphonates (N-BPs). This pathology occurs via bone and soft tissue mechanism. Zoledronic acid (ZA) is the most potent intravenous N-BP used to prevent bone loss in patients with bone dysfunction. The objective of this in vitro study was to evaluate the role of different ZA concentrations on the cells from human oral cavity, as well as the potential of plasma rich in growth factors (PRGF) to overcome the negative effects of this BP.
  
  
  METHODS
  Primary human gingival fibroblasts and primary human alveolar osteoblasts were used. Cell proliferation was evaluated by means of a fluorescence-based method. A colorimetric assay to detect DNA fragmentation undergoing apoptosis was used to determine cell death, and the expression of both NF-κB and pNF-κB were quantified by Western blot analysis.
  
  
  RESULTS
  ZA had a cytotoxic effect on both human gingival fibroblasts and human alveolar osteoblasts. This BP inhibits cell proliferation, stimulates apoptosis, and induces inflammation. However, the addition of PRGF suppresses all these negative effects of the ZA.
  
  
  CONCLUSIONS
  PRGF shows a cytoprotective role against the negative effects of ZA on primary oral cells.
  
  
  CONCLUSIONS
  At present, there is no definitive treatment for bisphosphonates-related osteonecrosis of the jaw (BRONJ), being mainly palliatives. Our results revealed that PRGF has a cytoprotective role in cells exposed to zoledronic acid, thus providing a reliable adjunctive therapy for the treatment of BRONJ pathology.
authors.affiliation: Foundation Eduardo Anitua, Jacinto Quincoces, 39, 01007, Vitoria, Spain.|Laboratory of Regenerative Medicine, Biotechnology Institute (BTI), Vitoria, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Anitua
authors.affiliation: Laboratory of Regenerative Medicine, Biotechnology Institute (BTI), Vitoria, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Zalduendo
authors.affiliation: Laboratory of Regenerative Medicine, Biotechnology Institute (BTI), Vitoria, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Troya
authors.affiliation: Foundation Eduardo Anitua, Jacinto Quincoces, 39, 01007, Vitoria, Spain. gorka.orive@ehu.es.|Laboratory of Regenerative Medicine, Biotechnology Institute (BTI), Vitoria, Spain. gorka.orive@ehu.es.
authors.forename: Gorka
authors.initials: G
authors.lastname: Orive
mesh_terms: D000539:Alveolar Process / Q000166:cytology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D050071:Bone Density Conservation Agents / Q000009:adverse effects*; D049109:Cell Proliferation / Q000187:drug effects*; D004164:Diphosphonates / Q000009:adverse effects*; D005347:Fibroblasts / Q000187:drug effects*; D005881:Gingiva / Q000166:cytology; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects*; D066298:In Vitro Techniques; D007249:Inflammation / Q000139:chemically induced; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects*; D010949:Plasma; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D036341:Intercellular Signaling Peptides and Proteins; D016328:NF-kappa B; D000077211:Zoledronic Acid
keywords: Apoptosis; Bisphosphonates; Inflammation; Oral cells; Plasma rich in growth factors; Zoledronic acid