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

Autor(es)

Petean, I. B. F. ^[1] ; Almeida-Junior, L. A. ^[1] ; Arnez, M. F. M. ^[1] ; Queiroz, A. M. ^[1] ; Silva, R. A. B. ^[1] ; Silva, L. A. B. ^[1] ; Faccioli, L. H. ^[2] ; Paula-Silva, F. W. G. ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Dent Ribeirao Preto, Dept Pediat Dent, Ave Cafe S-N, BR-14040904 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Anal Clin Toxicol & Bromatol, Lab Inflamacao & Imunol Parasitoses, Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: International Endodontic Journal; v. 54, n. 8, p. 1289-1299, AUG 2021.
• Citações Web of Science: 1

Resumo

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 mu g mu L-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 (alpha = 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 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. (AU)

• Processo FAPESP: 10/17611-4 - Mecanismos envolvidos na modulação da via 5-lipoxigenase na lesão periapical experimentalmente induzida
• Beneficiário: Francisco Wanderley Garcia de Paula e Silva
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 13/09595-7 - Papel dos inibidores seletivo e não-seletivo da enzima ciclooxigenase-2 e da enzima 5-lipoxigenase na osteoclastogênese no tratamento da lesão periapical experimental
• Beneficiário: Igor Bassi Ferreira Petean
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica