Dual Role of 5-Lipoxygenase in Osteoclastogenesis in Bacterial-induced Apical Periodontitis

Author(s)

Garcia Paula-Silva, Francisco Wanderley ^{[1, 2]} ; Ferreira Petean, Igor Bassi ^[1] ; Bezerra da Silva, Lea Assed ^[1] ; Faccioli, Lucia Helena ^[2]

Affiliation

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Sch Dent Ribeirao Preto, Dept Pediat Clin, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Anal Clin Toxicol & Bromatol, Lab Inflamacao & Imunol Parasitoses, Sao Paulo - Brazil

• Document type: Journal article
• Source: JOURNAL OF ENDODONTICS; v. 42, n. 3, p. 447-454, MAR 2016.
• Web of Science Citations: 5

Abstract

Introduction: 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 5-1.0 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. (AU)

• FAPESP's process: 10/17611-4 - Mechanisms involved in the regulation of 5-lipoxygenase pathway in experimentally-induced apical periodontitis
• Grantee: Francisco Wanderley Garcia de Paula e Silva
• Support Opportunities: Research Grants - Young Investigators Grants