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

AIM To evaluate the efficacy of selective and non-selective 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 (1.0µg / µL) 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), or Indomethacin, a non-selective COX-2 inhibitor (5 mg / kg), 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), while 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 Selective COX-2 inhibitor Celecoxib reduced osteoclastogenic signaling and activity that dampened bone resorption in LPS-induced apical periodontitis in mice, with greater efficacy than non-selective inhibitor Indomethacin.