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-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.