Periapical bone response to bacterial lipopolysaccharide is shifted upon cyclooxygenase blockage

Author(s)

Ribeiro-Santos, Fernanda Regina ^{[1, 2]} ; da Silva, Geyson Galo ^[1] ; Ferreira Petean, Igor Bassi ^[1] ; Manfrin Arnez, Maya Fernanda ^[1] ; Bezerra da Silva, Lea Assed ^[1] ; Faccioli, Lucia Helena ^[3] ; Garcia Paula-Silva, Francisco Wanderley ^{[1, 3]}

Affiliation

^[1] Univ Sao Paulo, Fac Odontol Ribeirao Preto, Dept Clin Infantil, Ribeirao Preto, SP - Brazil

^[2] Univ Pernambuco, Arco Verde, PE - Brazil

^[3] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Anal Clin Toxicol & Bromatol, Lab Inflamacao & Imunol Parasitoses, Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Journal of Applied Oral Science; v. 27, 2019.
• Web of Science Citations: 0

Abstract

Abstract Objectives: Infection, inflammation and bone resorption are closely related events in apical periodontitis development. Therefore, we sought to investigate the role of cyclooxygenase (COX) in osteoclastogenesis and bone metabolism signaling in periapical bone tissue after bacterial lipopolysaccharide (LPS) inoculation into root canals. Methodology: Seventy two C57BL/6 mice had the root canals of the first molars inoculated with a solution containing LPS from E. coli (1.0 mg/mL) and received selective (celecoxib) or non-selective (indomethacin) COX-2 inhibitor. After 7, 14, 21 and 28 days the animals were euthanized and the tissues removed for total RNA extraction. Evaluation of gene expression was performed by qRT-PCR. Statistical analysis was performed using analysis of variance (ANOVA) followed by post-tests (α=0.05). Results: LPS induced expression of mRNA for COX-2 (Ptgs2) and PGE2 receptors (Ptger1, Ptger3 and Ptger4), indicating that cyclooxygenase is involved in periapical response to LPS. A signaling that favours bone resorption was observed because Tnfsf11 (RANKL), Vegfa, Ctsk, Mmp9, Cd36, Icam, Vcam1, Nfkb1 and Sox9 were upregulated in response to LPS. Indomethacin and celecoxib differentially modulated expression of osteoclastogenic and other bone metabolism genes: celecoxib downregulated Igf1r, Ctsk, Mmp9, Cd36, Icam1, Nfkb1, Smad3, Sox9, Csf3, Vcam1 and Itga3 whereas indomethacin inhibited Tgfbr1, Igf1r, Ctsk, Mmp9, Sox9, Cd36 and Icam1. Conclusions: We demonstrated that gene expression for COX-2 and PGE2 receptors was upregulated after LPS inoculation into the root canals. Additionally, early administration of indomethacin and celecoxib (NSAIDs) inhibited osteoclastogenic signaling. The relevance of the cyclooxygenase pathway in apical periodontitis was shown by a wide modulation in the expression of genes involved in both bone catabolism and anabolism. (AU)

• FAPESP's process: 13/09595-7 - The role of selective and non-selective inhibitors enzyme cyclooxygenase-2 and 5-lipoxygenase enzyme in osteoclastogenesis after the development of experimental periapical
• Grantee: IGOR BASSI FERREIRA PETEAN
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• 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