Celecoxib treatment dampens LPS-induced periapical bone resorption in a mouse model.

AIM: To evaluate the efficacy of selective and nonselective inhibitors of cyclooxygenase-2 enzymes in the treatment of experimental apical periodontitis induced by bacterial lipopolysaccharide (LPS) in vivo in a mouse model. METHODOLOGY: Thirty-six C57BL/6 mice were used. After access cavity preparation, a solution containing E. coli LPS (1.0 µg µL-1 ) was inoculated into the root canals of the mandibular and maxillary right first molars (n = 72) After 30 days, apical periodontitis was established and the animals were systemically treated with celecoxib, a selective COX-2 inhibitor (15 mg kg-1 ), or indomethacin, a nonselective COX-2 inhibitor (5 mg kg-1 ), for 7 and 14 days. Blocks containing teeth and bone were removed for histopathological and histometric analyses (haematoxylin and eosin), evaluation of osteoclasts numbers (tartrate-resistant acid phosphatase enzyme - TRAP) and immunohistochemistry for RANK, RANKL and OPG. Gene expression was performed using reverse transcription and real-time polymerase chain reaction (qRT-PCR) for RANK, RANKL, OPG, TRAP, MMP-9, cathepsin K and calcitonin receptor. Histopathological, histometric, TRAP, immunohistochemistry and qRT-PCR data were evaluated using Kruskal-Wallis followed by Dunn's test (α = 0.05). RESULTS: Systemic administration of celecoxib for 7 and 14 days prevented periapical bone resorption (P < 0.0001), differently from indomethacin that exacerbated bone resorption at 7 days (P < 0.0001) or exerted no effect at 14 days (P = 0.8488). Celecoxib treatment reduced osteoclast formation in apical periodontitis, regardless of the period of treatment (P < 0.0001 for 7 days and P = 0.026 for 14 days). Administration of celecoxib or indomethacin differentially modulated the expression of genes involved in bone resorption. At 7 days, celecoxib and indomethacin treatment significantly inhibited expression of mRNA for cathepsin K (P = 0.0005 and P = 0.016, respectively) without changing TRAP, MMP-9 and calcitonin receptor gene expression. At 14 days, celecoxib significantly inhibited expression of mRNA for MMP-9 (P < 0.0001) and calcitonin receptor (P = 0.004), whilst indomethacin exerted no effect on MMP-9 (P = 0.216) and calcitonin receptor (P = 0.971) but significantly augmented cathepsin K gene expression (P = 0.001). CONCLUSIONS: The selective COX-2 inhibitor celecoxib reduced osteoclastogenic signalling and activity that dampened bone resorption in LPS-induced apical periodontitis in mice, with greater efficacy than the nonselective inhibitor indomethacin.

Association between genetic polymorphisms in the promoter region of the defensin beta 1 gene and persistent apical periodontitis.

AIM: To evaluate the association between the promoter region of defensin beta 1 (DEFB1) genetic polymorphisms and persistent apical periodontitis (PAP) in Brazilian patients. METHODOLOGY: Seventy-three patients with post-treatment PAP (PAP group) and 89 patients with root filled teeth with healed and healthy periradicular tissues (healed group) were included (all teeth had apical periodontitis lesions at the beginning of the treatment). Patients who had undergone at least 1 year of follow-up after root canal treatment were recalled, and their genomic DNA was extracted from saliva. Two single nucleotide polymorphisms (SNPs) in DEFB1 at the g. -52G>A (rs1799946) and g. -20G>A (rs11362) positions were analysed using real-time polymerase chain reaction. The chi-squared test was performed, and the odds ratios were calculated using Epi Info 3.5.2. Logistic regression analysis in the codominant model, using the time of follow-up as a variable, was used to evaluate the SNP-SNP interaction. All tests were performed with an established alpha of 0.05 (P = 0.05). RESULTS: For the rs11362 polymorphism in the codominant and recessive models, patients who carried two copies of the T allele had a significantly lower risk of developing PAP (P = 0.040 and P = 0.031, respectively). For the rs1799946 polymorphism in DEFB1 in the codominant and recessive models, carrying one copy of the T allele significantly increased the risk of developing PAP (P = 0.007 and P = 0.031, respectively). In the logistic regression, both polymorphisms were associated with PAP as well as the SNP-SNP interaction (P < 0.0001). CONCLUSIONS: Polymorphisms in DEFB1 genes were associated with the development of post-treatment persistent apical periodontitis.