Silva Clara Marina Pereira Cavalcanti, Massoni Vivian Vicentin, Araujo Lisa Danielly Curcino, Lima Ricardo Barbosa, de Freitas Miranda-Filho Aluísio Eustáquio, Pucinelli Carolina Maschietto, Lucisano Marília Pacífico, Nelson-Filho Paulo, Consolaro Alberto, da Silva Raquel Assed Bezerra, da Silva Léa Assed Bezerra
Graduate Program in Pediatric Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
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.
Clin Oral Investig. 2025 Mar 1;29(3):166. doi: 10.1007/s00784-025-06246-z.
To evaluate and correlate the expression of REDOX enzymes and NET markers during the development of periapical lesions (PLs) in mice.
PLs were experimentally induced by pulpal exposure of first molars. In all, 42 mice were involved in a negative control and five periods (after 2, 5, 7, 21 and 42 days) (n = 7 in each period). Microscopic analysis of the specimens was carried out, considering inflammatory response and the PL area (mm). In addition, qRT-PCR (genes) and immunohistochemistry assay (proteins) were performed for REDOX enzymes (NOS2, SOD1, CAT, and GSR) and NET markers (MPO, H3CIT, and ELANE). The significance level was set at 5%.
Pulpal exposure led to the formation of PLs, especially after 21 and 42 days, when there was significantly increased bone resorption compared to previous periods (P < 0.001). There was an increased expression of all REDOX enzymes, as well as MPO and H3CIT markers after pulpal exposure in at least one time point in relation to the negative control, especially after 5 days (P = 0.002 or less). NOS2, SOD1, ELANE and H3CIT were significantly correlated with the PL area (P < 0.05). In addition, there was also a correlation between REDOX enzymes and NET markers (P < 0.05), such as all REDOX enzymes with H3CIT, CAT and GSR with MPO, and CAT and GSR with ELANE (P < 0.05).
Pulpal exposure modified the expression of REDOX enzymes and NET markers throughout the development of PLs, as well as some of these enzymes and markers were correlated, which may suggest the association of different molecular pathways.
The association between REDOX activity and NETs, including their molecular signaling, may modify the development of PLs after pulpal exposure and should be investigated as a possible therapeutic target in periapical bone repair.
评估并关联小鼠根尖周病变(PLs)发展过程中氧化还原酶和中性粒细胞胞外陷阱(NET)标志物的表达。
通过暴露第一磨牙牙髓实验性诱导PLs。总共42只小鼠参与阴性对照及五个时间段(2、5、7、21和42天后)(每个时间段n = 7)。对标本进行显微镜分析,考量炎症反应和PL面积(mm)。此外,针对氧化还原酶(NOS2、SOD1、CAT和GSR)和NET标志物(MPO、H3CIT和ELANE)进行定量逆转录聚合酶链反应(qRT-PCR,基因)和免疫组织化学检测(蛋白质)。显著性水平设定为5%。
牙髓暴露导致PLs形成,尤其是在21天和42天后,与先前时间段相比,此时骨吸收显著增加(P < 0.001)。与阴性对照相比,牙髓暴露后至少在一个时间点所有氧化还原酶以及MPO和H3CIT标志物的表达均增加,尤其是在5天后(P = 0.002或更低)。NOS2、SOD1、ELANE和H3CIT与PL面积显著相关(P < 0.05)。此外,氧化还原酶与NET标志物之间也存在相关性(P < 0.05),例如所有氧化还原酶与H3CIT、CAT和GSR与MPO,以及CAT和GSR与ELANE(P < 0.05)。
牙髓暴露在PLs的整个发展过程中改变了氧化还原酶和NET标志物的表达,并且其中一些酶和标志物存在相关性,这可能提示不同分子途径之间的关联。
氧化还原活性与NETs之间的关联,包括它们的分子信号传导,可能会改变牙髓暴露后PLs的发展,应作为根尖周骨修复中可能的治疗靶点进行研究。