Huang Fangting, Su Zhifei, Zhou Fangjie, Wu Yajie, Li Jiyao, Ren Biao
State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China.
Department of Preventive Dentistry, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-Sen University, Guangzhou, Guangdong, China.
Infect Immun. 2025 Mar 11;93(3):e0041024. doi: 10.1128/iai.00410-24. Epub 2025 Feb 20.
The postmenopausal population usually suffers from more severe periodontal disease than non-menopausal women due to the decrease and low levels of estrogen, especially β-estradiol (E2). While additional estrogen therapy can effectively relieve alveolar bone resorption, this suggests that estrogen has played an important role in the development of periodontitis. The integrity of the gingival epithelial barrier plays a key role in protecting gingival tissue from inflammatory injury caused by pathogens. However, it remains unclear whether estrogen can maintain the integrity of the gingival epithelial barrier to reduce inflammatory injury. Here, using an infection model established with lipopolysaccharide (LPS) in human gingival epithelial cells (hGECs) and ovariectomized or Sham mice, we assessed the protective effect of estrogen on the gingival barrier using qPCR, western blotting, immunohistochemistry, and transcriptome analysis. The results showed that estrogen restored epithelial barrier function to inhibit -LPS invasion and further downregulate the inflammatory reaction ( < 0.05) by upregulating expressions of tight junction proteins (such as JAM1 and OCLN) at mRNA and protein levels in both hGECs and ovariectomized or Sham mice ( < 0.05). Estrogen also protected against alveolar bone resorption and preserved barrier integrity in both ovariectomized and Sham mice ( < 0.05). In conclusion, E2 prevented the progression of gingival epithelial barrier damage and inflammation induced by -LPS by increasing the expression of tight junction proteins. The protective effect of estrogen on gingival epithelial barrier injury highlighted its potential application in treating periodontitis and inflammatory diseases involving epithelial barrier dysfunction.
绝经后人群通常比未绝经女性患有更严重的牙周疾病，这是由于雌激素尤其是β-雌二醇（E2）水平降低。虽然额外的雌激素治疗可以有效缓解牙槽骨吸收，这表明雌激素在牙周炎的发展中起重要作用。牙龈上皮屏障的完整性在保护牙龈组织免受病原体引起的炎症损伤方面起关键作用。然而，雌激素是否能维持牙龈上皮屏障的完整性以减少炎症损伤仍不清楚。在此，我们利用脂多糖（LPS）在人牙龈上皮细胞（hGECs）以及去卵巢或假手术小鼠中建立感染模型，通过定量聚合酶链反应（qPCR）、蛋白质印迹法、免疫组织化学和转录组分析评估雌激素对牙龈屏障的保护作用。结果表明，雌激素通过上调紧密连接蛋白（如连接黏附分子1和闭合蛋白）在mRNA和蛋白质水平的表达，恢复上皮屏障功能以抑制LPS侵袭，并进一步下调炎症反应（P<0.05），在hGECs以及去卵巢或假手术小鼠中均是如此（P<0.05）。雌激素还能预防去卵巢和假手术小鼠的牙槽骨吸收并维持屏障完整性（P<0.05）。总之，E2通过增加紧密连接蛋白的表达，阻止了由LPS诱导的牙龈上皮屏障损伤和炎症的进展。雌激素对牙龈上皮屏障损伤的保护作用突出了其在治疗牙周炎和涉及上皮屏障功能障碍的炎症性疾病中的潜在应用价值。
