Department of Pediatric Dentistry (DCI), School of Dentistry of Ribeirão Preto, University of São Paulo (FORP/USP), Avenida do Café, s/n, Vila Monte Alegre, Ribeirão Preto, São Paulo, Brazil.
Graduate Program in Pediatric Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
Clin Oral Investig. 2024 Apr 30;28(5):285. doi: 10.1007/s00784-024-05691-6.
To evaluate the effects of NLRP3 inflammasome inhibition or knockout in experimental apical periodontitis (AP) induced in mice.
The experimental AP was induced by pulpal exposure. To evaluate NLRP3-specific inhibitor medication (MCC950), WT mice received intraperitoneal injections, while the control received PBS (n = 10). In addition, to evaluate NLRP3 knockout, 35 wild-type (WT) and 35 NLRP3 mice were divided into a control group (without pulpal exposure, n = 5) and three experimental groups: after 2, 14 and 42 days after pulpal exposure (n = 10). Microscopic and molecular analyzes were carried out using a significance level of 5%.
Exposure to MCC950 did not affect the periapical lesion size after 14 days (P = 0.584). However, exposed mice had a lower expression of IL-1β, IL-18 and caspase-1 (P = 0.010, 0.016 and 0.002, respectively). Moreover, NLRP3 mice showed a smaller periapical lesion after 14 and 42 days (P = 0.023 and 0.031, respectively), as well as a lower expression of IL-1β after 42 days (P < 0.001), of IL-18 and caspase-1 after 14 (P < 0.001 and 0.035, respectively) and 42 days (P = 0.002 and 0.002, respectively). NLRP3 mice also showed a lower mRNA for Il-1β, Il-18 and Casp1 after 2 (P = 0.002, 0.036 and 0.001, respectively) and 14 days (P = 0.002, 0.002 and 0.001, respectively).
NLRP3 inflammasome inhibition or knockout can attenuate the inflammatory events that result in the periapical lesion (AP) formation after pulpal exposure in mice.
The NLRP3 inflammasome may be a therapeutic target for AP, and new approaches may verify the impact of its inhibition (through intracanal medications or filling materials) on the bone repair process and treatment success.
评估 NLRP3 炎性小体抑制或敲除对实验性根尖周炎（AP）的影响。
牙髓暴露诱导实验性 AP。为评估 NLRP3 特异性抑制剂（MCC950），WT 小鼠接受腹腔注射，而对照组接受 PBS（n = 10）。此外，为评估 NLRP3 敲除，35 只野生型（WT）和 35 只 NLRP3 小鼠分为对照组（无牙髓暴露，n = 5）和三个实验组：牙髓暴露后 2、14 和 42 天（n = 10）。采用 5%的显著水平进行显微镜和分子分析。
MCC950 暴露后 14 天对根尖病变大小无影响（P = 0.584）。然而，暴露的小鼠 IL-1β、IL-18 和 caspase-1 的表达水平较低（P = 0.010、0.016 和 0.002）。此外，NLRP3 小鼠在 14 和 42 天后根尖病变较小（P = 0.023 和 0.031），42 天后 IL-1β 表达较低（P < 0.001），14 和 42 天后 IL-18 和 caspase-1 表达较低（P < 0.001 和 0.035）。NLRP3 小鼠在 2 天和 14 天的 Il-1β、Il-18 和 Casp1 的 mRNA 水平也较低（P = 0.002、0.036 和 0.001）和 14 天（P = 0.002、0.002 和 0.001）。
NLRP3 炎性小体的抑制或敲除可减轻牙髓暴露后小鼠根尖病变形成中的炎症事件。
NLRP3 炎性小体可能是 AP 的治疗靶点，新方法可能验证其抑制（通过根管内药物或填充材料）对骨修复过程和治疗成功的影响。
