title: Dual Role of 5-Lipoxygenase in Osteoclastogenesis in Bacterial-induced Apical Periodontitis.
abstract: BACKGROUND
  The aim of this study was to evaluate the role of 5-lipoxigenase (5-LO) in the signaling for osteoclast formation and bone resorption in apical periodontitis (AP) after root canal contamination with oral bacteria.
  
  
  METHODS
  AP was experimentally induced in C57BL/6 mice because of contamination of the root canals left open to the oral environment. MK886 was used as a systemic inhibitor of 5-LO (5 mg/kg, daily). After 7, 14, 21, and 28 days, the animals were euthanized, and tissues were removed for gene evaluation by quantitative reverse transcriptase polymerase chain reaction, histologic analysis, and tartrate-resistant acid phosphatase staining.
  
  
  RESULTS
  Root canal contamination induced the expression of messenger RNA for 5-LO and leukotriene B4 receptors BLT1 and BLT2. The administration of the 5-LO inhibitor reduced early receptor activator of nuclear factor kappa-B and receptor activator of nuclear factor kappa-B ligand synthesis but augmented late receptor activator of nuclear factor kappa-B ligand and osteoprotegerin expression during the course of AP development. Interestingly, long-term inhibition of 5-LO resulted in increased bone resorption and induced tartrate-resistant acid phosphatase-positive osteoclast formation. The divergent findings related to 5-LO inhibition in osteoclastogenesis signaling, osteoclast formation, and bone resorption were accompanied by differently regulated inflammatory gene expression. Il1b, Il11, Ccl3, Ccl7, and Spp were down-regulated by the 5-LO inhibitor in early AP, but later on Il11, Ccl3, Cxcl9, Cxcl15, and Spp were up-regulated.
  
  
  CONCLUSIONS
  5-LO presented a dual role in osteoclastogenesis during the course of AP development. Early on, osteoclastogenesis signaling was down-regulated by the inhibition of 5-LO, but long-term inhibition failed to prevent synthesis of catabolic mediators that resulted in increased bone loss.
authors.affiliation: Department of Pediatric Clinics, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil; Laboratório de Inflamação e Imunologia das Parasitoses, Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil. Electronic address: franciscogarcia@usp.br.
authors.forename: Francisco Wanderley Garcia
authors.initials: FW
authors.lastname: Paula-Silva
authors.affiliation: Department of Pediatric Clinics, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Igor Bassi Ferreira
authors.initials: IB
authors.lastname: Petean
authors.affiliation: Department of Pediatric Clinics, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Léa Assed Bezerra
authors.initials: LA
authors.lastname: da Silva
authors.affiliation: Laboratório de Inflamação e Imunologia das Parasitoses, Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Lúcia Helena
authors.initials: LH
authors.lastname: Faccioli
mesh_terms: D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D001862:Bone Resorption / Q000382:microbiology / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003786:Dental Pulp Cavity / Q000382:microbiology / Q000473:pathology; D004195:Disease Models, Animal; D015536:Down-Regulation; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D010012:Osteogenesis / Q000502:physiology*; D010485:Periapical Periodontitis / Q000201:enzymology* / Q000382:microbiology / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016207:Cytokines; D016859:Lipoxygenase Inhibitors; D001094:Arachidonate 5-Lipoxygenase
keywords: 5-lipoxygenase; apical periodontitis; bone resorption; cytokines; osteoclast; osteoclastogenesis