title: In vitro comparison of new bisphosphonic acids and zoledronate effects on human gingival fibroblasts viability, inflammation and matrix turnover.
abstract: OBJECTIVE
  Bisphosphonates (BPs) are drugs clinically used in resorptive diseases. It was already proved that some clinically relevant BPs can inhibit a class of enzymes called matrix metalloproteinases (MMPs), required during tissue remodelling. Combining the arylsulfonamide function with the bisphosphonic group, several compounds were synthesized to obtain selective inhibitors of MMPs. The aim of the present study was to compare the effect of zoledronic acid (ZA), the most potent bisphosphonate available as therapy, with new sulfonamide containing BPs in an in vitro model of human gingival fibroblasts (HGFs).
  
  
  METHODS
  Western blot was used to measure procollagen I, β1 integrin MMP-8 and MMP-9, phase contrast and MTT for cell viability; L-lactate-dehydrogenase (LDH) measurement was performed for toxicity evaluation and ELISA for prostaglandin E2(PGE2) secretion assessment.
  
  
  RESULTS
  When compared with ZA, the treatment with the newly synthesized compounds shows increasing viability, procollagen I expression and decreased expression of β1 integrin in HGFs. Higher levels of released LDH, PGE2and MMP-9 expression are recorded in ZA-treated HGFs. Increased levels of MMP-8 are recorded in newly synthesized compounds-treated samples.
  
  
  CONCLUSIONS
  These findings allowed to conclude that new tested BPs did not affect HGFs viability and adhesion, did not induce cellular toxicity, were not responsible for inflammatory event induction and could preserve the physiological matrix turnover.
  
  
  CONCLUSIONS
  It could be hypothesized that the new molecules were better tolerated by soft tissues, resulting in lesser side effects.
authors.affiliation: Section of Human Anatomy, Department of Pharmacy, University "G. d'Annunzio", Chieti-Pescara, via dei Vestini 31, 66100, Chieti, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: De Colli
authors.affiliation: Department of Pharmacy-Drug Sciences, University "Aldo Moro", Bari, via Orabona 4, 70110, Bari, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Tortorella
authors.affiliation: Section of Human Anatomy, Department of Pharmacy, University "G. d'Annunzio", Chieti-Pescara, via dei Vestini 31, 66100, Chieti, Italy.
authors.forename: Guya Diletta
authors.initials: GD
authors.lastname: Marconi
authors.affiliation: Section of Human Anatomy, Department of Pharmacy, University "G. d'Annunzio", Chieti-Pescara, via dei Vestini 31, 66100, Chieti, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Agamennone
authors.affiliation: Section of Human Anatomy, Department of Pharmacy, University "G. d'Annunzio", Chieti-Pescara, via dei Vestini 31, 66100, Chieti, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Campestre
authors.affiliation: Departments of Tumor Biology, Moffitt Cancer Center and Research Institute, 12902 Magnolia Dr., SRB-3, Tampa, FL, USA.
authors.forename: Marilena
authors.initials: M
authors.lastname: Tauro
authors.affiliation: Section of Human Anatomy, Department of Pharmacy, University "G. d'Annunzio", Chieti-Pescara, via dei Vestini 31, 66100, Chieti, Italy.
authors.forename: Amelia
authors.initials: A
authors.lastname: Cataldi
authors.affiliation: Section of Human Anatomy, Department of Pharmacy, University "G. d'Annunzio", Chieti-Pescara, via dei Vestini 31, 66100, Chieti, Italy. s.zara@unich.it.
authors.forename: Susi
authors.initials: S
authors.lastname: Zara
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D050071:Bone Density Conservation Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004164:Diphosphonates / Q000138:chemical synthesis / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects*; D005881:Gingiva / Q000166:cytology*; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D066298:In Vitro Techniques; D007249:Inflammation; D008964:Molar, Third; D000077211:Zoledronic Acid
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid
keywords: Bisphosphonate; Human gingival fibroblast; Metalloproteinase; Zoledronate