Department of Pediatric Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil; Laboratório de Inflamação e Imunologia das Parasitoses, Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Department of Pediatric Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Arch Oral Biol. 2020 Apr;112:104670. doi: 10.1016/j.archoralbio.2020.104670. Epub 2020 Feb 6.
To investigate the regulation of inflammatory and osteoclastogenic signaling by 5-lipoxygenase (5-LO) in apical periodontitis induced by oral contamination of dental root canals in mice.
Apical periodontitis was induced in 5-lipoxygenase enzyme knockout (129-Alox5) and 129 wild-type mice (n = 96) by exposure of the dental root canal to the oral cavity. After 7, 14, 21, and 28 days, the animals were euthanized and the tissues removed (n = 12 teeth per period) for histopathological and histometric analyses (hematoxylin and eosin [HE]), evaluation of osteoclastogenic activity (tartrate-resistant acid phosphatase enzyme [TRAP]), and determination of inflammatory and osteoclastogenic signaling (qRT-PCR).
Oral contamination of dental root canals induced recruitment of neutrophils and osteoclasts to the periodontal ligament, resulting in bone resorption. Absence of 5-LO did not impair neutrophil recruitment while osteoclastic formation was increased. Nonetheless, early bone resorption progressed similarly to lesions in wild-type animals. Interestingly, in the absence of 5-LO, the synthesis of mRNAs for cytokines, chemokines, and their receptors was significantly reduced while that of regulators of osteoclastogenesis (RANK, RANKL, and OPG) was increased in comparison with the corresponding levels in wild-type animals.
The 5-LO pathway plays a role in the stimulation of inflammatory mediator synthesis and inhibition of osteoclastogenesis in apical periodontitis in mice. However, the paradoxical inflammatory-osteoclastogenic signaling did not impair inflammatory cell recruitment and bone resorption during early development of the disease.
研究 5-脂氧合酶（5-LO）在口腔污染根管引起的小鼠根尖周炎中的炎症和破骨细胞生成信号的调节作用。
通过将牙髓暴露于口腔中，在 5-脂氧合酶酶敲除（129-Alox5）和 129 野生型小鼠（n = 96）中诱导根尖周炎。在 7、14、21 和 28 天后，处死动物并取出组织（每个时期 n = 12 颗牙）进行组织病理学和组织学分析（苏木精和伊红[HE]）、破骨细胞生成活性评估（抗酒石酸酸性磷酸酶酶[TRAP]）和炎症和破骨细胞生成信号的测定（qRT-PCR）。
口腔污染根管诱导牙周韧带中中性粒细胞和破骨细胞的募集，导致骨吸收。5-LO 缺失不影响中性粒细胞的募集，但破骨细胞形成增加。然而，早期骨吸收的进展与野生型动物的病变相似。有趣的是，在缺乏 5-LO 的情况下，细胞因子、趋化因子及其受体的 mRNA 合成显著减少，而破骨细胞生成调节剂（RANK、RANKL 和 OPG）的合成增加与野生型动物的相应水平相比。
5-LO 途径在小鼠根尖周炎中炎症介质合成的刺激和破骨细胞生成的抑制中起作用。然而，在疾病早期发展过程中，这种矛盾的炎症-破骨细胞生成信号并没有削弱炎症细胞的募集和骨吸收。
