Department of Pediatric Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brasil.
Laboratório de Inflamação e Imunologia das Parasitoses, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brasil.
Int Endod J. 2021 Aug;54(8):1289-1299. doi: 10.1111/iej.13472. Epub 2021 May 28.
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.
Thirty-six C57BL/6 mice were used. After access cavity preparation, a solution containing E. coli LPS (1.0 µg 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 nonselective 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).
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).
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.
评估环氧化酶-2 酶的选择性和非选择性抑制剂在体内细菌脂多糖 (LPS) 诱导的实验性根尖周炎治疗中的疗效，建立一个小鼠模型。
使用 36 只 C57BL/6 小鼠。在制备开髓腔后，将含有 E. coli LPS（1.0μgμL）的溶液接种到下颌和上颌右侧第一磨牙的根管中（n=72）。30 天后，建立根尖周炎，动物全身接受塞来昔布（一种选择性 COX-2 抑制剂，15mgkg）或吲哚美辛（一种非选择性 COX-2 抑制剂，5mgkg）治疗 7 天和 14 天。取出含牙和骨的块进行组织病理学和组织学分析（苏木精和伊红）、破骨细胞数量评估（抗酒石酸酸性磷酸酶酶-TRAP）和 RANK、RANKL 和 OPG 的免疫组织化学。使用逆转录和实时聚合酶链反应（qRT-PCR）对 RANK、RANKL、OPG、TRAP、MMP-9、组织蛋白酶 K 和降钙素受体进行基因表达。使用 Kruskal-Wallis 检验 followed by Dunn's test（α=0.05）评估组织病理学、组织学、TRAP、免疫组织化学和 qRT-PCR 数据。
塞来昔布连续治疗 7 天和 14 天可预防根尖周骨吸收（P<0.0001），与吲哚美辛不同，吲哚美辛在第 7 天加剧了骨吸收（P<0.0001）或在第 14 天没有影响（P=0.8488）。塞来昔布治疗可减少根尖周炎中的破骨细胞形成，无论治疗时间如何（7 天 P<0.0001，14 天 P=0.026）。塞来昔布和吲哚美辛的给药以不同的方式调节了参与骨吸收的基因的表达。在第 7 天，塞来昔布和吲哚美辛治疗显著抑制了组织蛋白酶 K（P=0.0005 和 P=0.016）mRNA 的表达，而不改变 TRAP、MMP-9 和降钙素受体基因的表达。在第 14 天，塞来昔布显著抑制了 MMP-9（P<0.0001）和降钙素受体（P=0.004）mRNA 的表达，而吲哚美辛对 MMP-9（P=0.216）和降钙素受体（P=0.971）没有影响，但显著增加了组织蛋白酶 K 基因的表达（P=0.001）。
选择性 COX-2 抑制剂塞来昔布减少了 LPS 诱导的根尖周炎中的破骨细胞生成信号和活性，其疗效优于非选择性抑制剂吲哚美辛。
