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 PGE
2
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 PGE
2
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.