Evaluation of Endoplasmic Reticulum Stress Response in the Pathogenesis of Periodontal Disease
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 72
- 试验地点
- 1
- 主要终点
- GCF, Gingival tissue levels of GRP78, PERK, IRE1, ATF6, MANF, CRELD2, and TNF-α.
研究概览
简要总结
Periodontal disease causes inflammation and damage to the tissues that support the teeth. This study looks at whether stress inside gum cells contributes to this damage. Cells have a stress response system that helps them deal with damaged or misfolded proteins. This study measured several markers of this cell stress response (called GRP78, PERK, IRE1, ATF6, MANF, CRELD2) along with a marker of inflammation (TNF-α). These were measured in fluid collected from around the teeth and in small samples of gum tissue.
Researchers compared 72 healthy adults who did not smoke, divided into three equal groups: people with healthy gums, people with mild gum inflammation (gingivitis), and people with a more advanced form of gum disease (periodontitis). The results showed that markers of cell stress were higher in people with periodontitis compared to the other two groups, both in the fluid around the teeth and in the gum tissue itself. This suggests that cell stress inside gum tissue may play a role in the inflammation and tissue breakdown seen in periodontitis. These findings may help researchers better understand what drives gum disease and could guide future work on new ways to detect or treat it.
详细描述
Periodontal disease will range from gingivitis, a mild and reversible gum inflammation, to periodontitis, a more advanced form that will cause irreversible destruction of the bone and tissue supporting the teeth and may lead to tooth loss if left untreated. A cellular process known as endoplasmic reticulum (ER) stress will be increasingly linked to chronic inflammatory diseases. When cells are exposed to stress, misfolded proteins will accumulate inside the endoplasmic reticulum, and cells will activate a protective mechanism called the unfolded protein response (UPR) to restore normal function. The UPR will operate through three main pathways controlled by the proteins PERK, IRE1, and ATF6. This study will investigate whether markers of ER stress and the UPR, GRP78, PERK, IRE1, ATF6, MANF, and CRELD2 along with the inflammatory marker TNF-α, will be altered in individuals with periodontal disease, and whether these changes will be associated with inflammation severity and tissue destruction. The study will include 72 systemically healthy, non-smoking adults, divided into three equal groups of 24: periodontally healthy individuals, individuals with gingivitis, and individuals with stage III grade B periodontitis. From each participant, gingival crevicular fluid and gingival tissue samples will be collected. Protein levels will be measured using ELISA, and gene expression levels will be assessed using RT-qPCR. In the periodontitis group, total amounts of GRP78, IRE1, PERK, MANF, and CRELD2 in gingival crevicular fluid are expected to be significantly higher, while their concentrations are expected to be lower. Protein levels of IRE1, PERK, MANF, and CRELD2 in gingival tissue, along with gene expression levels of all markers studied, are expected to be significantly elevated. ATF6 is expected to show a distinct pattern, with decreased fluid levels but increased tissue gene expression.
These findings are expected to show that ER stress and UPR pathways will be more active in the gingival tissue of individuals with periodontitis, correlating with inflammation and tissue destruction. This will help researchers identify new biological markers for periodontal disease and support future research into treatments targeting cellular stress pathways.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Inclusion criteria for the Healthy Control group were: presence of ≥ 20 teeth in the mouth, probing pocket depth (PPD) ≤ 3 mm, the percentage of bleeding sites for the whole mouth < 10%, and, on radiographic examination, a distance of ≤ 3 mm between the cemento-enamel junction and the alveolar bone crest in 95% of all teeth. Inclusion criteria for the Gingivitis group were: presence of ≥ 20 teeth in the mouth, PPD ≤ 3 mm, % of bleeding sites for the whole mouth ≥ 10%, and, on radiographic examination, a distance of ≤ 3 mm between the cemento-enamel junction and the alveolar bone crest in 95% of all teeth. Inclusion criteria for the Stage 3 Periodontitis group were: presence of ≥ 15 teeth in the mouth, more than 30% of teeth affected by periodontal disease, affected teeth exhibiting probing depths of 6 mm or more and clinical attachment loss (CAL) of ≥ 5 mm, vertical bone loss of 3 mm or more, class 2 or 3 furcation involvement, and radiographic evidence of alveolar bone loss extending to the middle third and beyond (33%) in the relevant teeth
排除标准
- •Exclusion criteria for all groups were defined as: presence of any systemic disease, regular use of any medication, smoking, pregnancy or lactation, periodontal treatment within the last 6 months, antibiotic use within the last 6 months, and the presence of prosthetic restorations on the teeth to be sampled.
研究组 & 干预措施
periodontally healthy
periodontally healthy participants
gingivitis
patients with gingivitis
periodontitis
patients with periodontitis
结局指标
主要结局
GCF, Gingival tissue levels of GRP78, PERK, IRE1, ATF6, MANF, CRELD2, and TNF-α.
时间窗: From September 2025 to February 2026
Gene expression (RT-PCR, relative fold change via 2\^-ΔΔCT method) levels of GRP78, PERK, IRE1, ATF6, MANF, CRELD2, and TNF-α were measured in gingival tissue samples of participants. Protein levels of GRP78, PERK, IRE1, ATF6, MANF, CRELD2, and TNF-α in GCF and gingival tissue samples were measured by ELISA in study participants.
次要结局
未报告次要终点
研究者
Kubra Aral
Associate Professor
Inonu University