title: Immune cellular profile of bisphosphonate-related osteonecrosis of the jaw.
abstract: OBJECTIVE
  Characterize the cell profile and immunostaining of proinflammatory markers in an experimental model of bisphosphonate-related osteonecrosis of the jaw (BRONJ).
  
  
  METHODS
  Male Wistar rats (n = 6-7) were treated chronically with saline solution or zoledronic acid (ZA) at 0.04, 0.20, and 1.00 mg kg(-1) (1.4 × 10(-7) , 6.9 × 10(-6) , and 3.4 × 10(-5)  mol kg(-1) ), and subsequently, the first left inferior molar was extracted. Were performed counting of viable and empty osteocyte lacunae, viable and apoptotic osteoclasts, polymorphonuclear neutrophil, mast cells (toluidine blue), and the positive presence cells for CD68, tumor necrosis factor-alpha (TNF-α), IL (interleukin)-1β, inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-kB) and IL-18 binding protein (IL-18 bp).
  
  
  RESULTS
  BRONJ was showed in ZA treated with 0.20 and 1.00 mg kg(-1) . There is a dose dependent increase in percentage of empty osteocyte lacunae (P < 0.001) and apoptotic osteoclasts (P < 0.001), counting of total osteoclasts (P = 0.003), polymorphonuclear neutrophil cells (P = 0.009), cytoplasmic-positive cells of CD68 (P < 0.001), TNF-α (P = 0.001), IL-1β (P = 0.001), iNOS (P < 0.001), NF-kB (P = 0.006), and nuclear-positive cells of NF-kB (P = 0.011). Consequently, there is no difference in mast cells (P = 0.957), and IL-18 bp immunostaining decreases dose dependently (P = 0.005).
  
  
  CONCLUSIONS
  BRONJ is characterized by increases in immunostaining for proinflammatory markers and NF-kB and inversely associated with cells exhibiting IL-18 bp.
authors.affiliation: Department of Dental Clinic, Division of Oral Pathology, Faculty of Pharmacy, Dentistry and Nursing, Federal University of Ceara, Fortaleza, Ceara, Brazil. paulo_goberlanio@yahoo.com.br.
authors.forename: P G
authors.identifier: http://orcid.org/0000-0002-1513-9027
authors.initials: PG
authors.lastname: de Barros Silva
authors.affiliation: Department of Dental Clinic, Division of Oral Pathology, Faculty of Pharmacy, Dentistry and Nursing, Federal University of Ceara, Fortaleza, Ceara, Brazil.
authors.forename: C C
authors.initials: CC
authors.lastname: de Oliveira
authors.affiliation: Department of Biotechnology, Faculty of Biotechnology, Federal University of Ceara, Fortaleza, Ceara, Brazil.
authors.forename: Lac
authors.initials: L
authors.lastname: Brizeno
authors.affiliation: Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, Ceara, Brazil.
authors.forename: Dvt
authors.initials: D
authors.lastname: Wong
authors.affiliation: Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, Ceara, Brazil.
authors.forename: Rcp
authors.initials: R
authors.lastname: Lima Júnior
authors.affiliation: Department of Clinical Analysis, Faculty of Pharmacy, Dentistry and Nursing, Federal University of Ceara, Fortaleza, Ceara, Brazil.
authors.forename: R P
authors.initials: RP
authors.lastname: Gonçalves
authors.affiliation: Department of Dental Clinic, Division of Oral Pathology, Faculty of Pharmacy, Dentistry and Nursing, Federal University of Ceara, Fortaleza, Ceara, Brazil.
authors.forename: F B
authors.initials: FB
authors.lastname: Sousa
authors.affiliation: Department of Dental Clinic, Division of Oral Pathology, Faculty of Pharmacy, Dentistry and Nursing, Federal University of Ceara, Fortaleza, Ceara, Brazil.
authors.forename: Mrl
authors.initials: M
authors.lastname: Mota
authors.affiliation: Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, Ceara, Brazil.
authors.forename: R
authors.initials: R
authors.lastname: de Albuquerque Ribeiro
authors.affiliation: Department of Dental Clinic, Division of Oral Pathology, Faculty of Pharmacy, Dentistry and Nursing, Federal University of Ceara, Fortaleza, Ceara, Brazil.
authors.forename: Apnn
authors.initials: A
authors.lastname: Alves
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000276:immunology* / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D023421:Models, Animal; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015415:Biomarkers
keywords: IL-18 binding proteins; NF-kappa B; bisphosphonate-associated osteonecrosis of the jaw; interleukin-1; nitric oxide synthase type II; tumor necrosis factor-alpha