State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
Department of Stomatology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
J Periodontal Res. 2022 Jun;57(3):519-532. doi: 10.1111/jre.12981. Epub 2022 Feb 25.
The purpose of this study was to investigate whether soy isoflavone supplementation is effective in preventing periodontal destruction exacerbated by estrogen deficiency (ED) and its potential mechanism.
The progression of periodontitis is affected by host factors, such as smoking, diabetes mellitus, and steroid use. Bone loss in periodontitis can be aggravated by ED.
A rat model of experimental periodontitis (EP) with ED was established by silk ligature and inoculation with Porphyromonas gingivalis, and some EP rats were subjected to bilateral ovariectomy (OVX). The treatment groups received an intravenous injection of 17-β-estradiol (E B) or soy isoflavones (SI) by gavage. The rats were euthanized, and the maxillary jaws, gingiva, and serum were harvested. Tight junction protein and interleukin (IL)-17 expression, reactive oxygen species (ROS) level, and periodontal destruction were assessed. In addition, we determined whether grainyhead-like 2 (GRHL2) is required for enhancing the epithelial barrier by SI in an in vitro P. gingivalis infection model.
Estrogen deficiency impaired the expression of genes encoding tight junction proteins in the gingiva, increased IL-17 level, and accelerated alveolar bone resorption. SI treatment alleviated tight junction protein expression, decreased IL-17 and ROS levels, and prevented the absorption of alveolar bone. Furthermore, GRHL2 expression was significantly induced by SI in human oral keratinocytes-1 (HOK-1) cells; GRHL2 knockdown impaired the expression of OCLN and ZO-1 induced by SI treatment.
Soy isoflavones alleviates periodontitis in OVX rats, as observed by the increased expression of tight junction proteins, and reduced IL-17 level and alveolar bone loss. The in vitro studies suggested that the enhancement of oral epithelial barrier by SI treatment was partially dependent on GRHL2.
本研究旨在探讨大豆异黄酮补充剂是否能有效预防雌激素缺乏(ED)加重的牙周破坏及其潜在机制。
牙周炎的进展受宿主因素的影响,如吸烟、糖尿病和类固醇的使用。ED 可加重牙周炎中的骨丢失。
通过丝线结扎和接种牙龈卟啉单胞菌建立 ED 大鼠实验性牙周炎(EP)模型,并对部分 EP 大鼠进行双侧卵巢切除术(OVX)。实验组大鼠通过灌胃接受 17-β-雌二醇(E2B)或大豆异黄酮(SI)治疗。处死大鼠,采集上颌骨、牙龈和血清。评估紧密连接蛋白和白细胞介素(IL)-17 的表达、活性氧(ROS)水平和牙周破坏。此外,我们还在牙龈卟啉单胞菌感染的体外模型中,确定了 SI 是否通过颗粒头样蛋白 2(GRHL2)增强上皮屏障。
ED 降低了牙龈中编码紧密连接蛋白的基因表达,增加了 IL-17 水平,并加速了牙槽骨吸收。SI 治疗可改善紧密连接蛋白的表达,降低 IL-17 和 ROS 水平,并防止牙槽骨吸收。此外,SI 可显著诱导人口腔角质形成细胞-1(HOK-1)细胞中 GRHL2 的表达;GRHL2 敲低可削弱 SI 治疗诱导的 OCLN 和 ZO-1 的表达。
大豆异黄酮通过增加紧密连接蛋白的表达,降低 IL-17 水平和牙槽骨丢失,缓解 OVX 大鼠的牙周炎。体外研究表明,SI 治疗增强口腔上皮屏障的作用部分依赖于 GRHL2。