Endoplasmic Reticulum Stress Response in Periodontal Disease

NCT07751419 | Completed

• 1 other identifier: IU-2025-4339
• Study Type: observational
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Periodontitis; Gingivitis

Keywords

endoplasmic reticulum; ER stress; Unfolded Protein Response; Periodontal Inflammation; Gingival Crevicular Fluid; Gingiva

Outcome Measures

Primary Outcomes (1)

• GCF, Gingival tissue levels of GRP78, PERK, IRE1, ATF6, MANF, CRELD2, and TNF-α.

  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.

  From September 2025 to February 2026

Study Arms (3)

periodontally healthy

periodontally healthy participants

gingivitis

patients with gingivitis

periodontitis

patients with periodontitis

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adults aged 18 to 65 years attending the periodontology clinic were enrolled and classified into three groups based on clinical periodontal parameters according to the 2017 World Workshop classification: periodontal health, gingivitis, and periodontitis (Stage III). Exclusion criteria included any systemic disease, regular medication use, smoking, pregnancy or lactation, periodontal treatment within the past 6 months, antibiotic use within the past 6 months, and presence of prosthetic restorations on the teeth to be sampled. A total of 72 participants (24 per group; 36 male, 36 female) were included.

Sponsors & Collaborators

• Inonu University: lead

Study Sites (1)

Kubra Aral

Malatya, 44100, Turkey (Türkiye)

Location

Related Publications (4)

• Teles R, Sakellari D, Teles F, Konstantinidis A, Kent R, Socransky S, Haffajee A. Relationships among gingival crevicular fluid biomarkers, clinical parameters of periodontal disease, and the subgingival microbiota. J Periodontol. 2010 Jan;81(1):89-98. doi: 10.1902/jop.2009.090397.

  PMID: 20059421 BACKGROUND

• Jiang M, Li Z, Zhu G. The role of endoplasmic reticulum stress in the pathophysiology of periodontal disease. J Periodontal Res. 2022 Oct;57(5):915-932. doi: 10.1111/jre.13031. Epub 2022 Jul 12.

  PMID: 35818935 BACKGROUND

• Walter P, Ron D. The unfolded protein response: from stress pathway to homeostatic regulation. Science. 2011 Nov 25;334(6059):1081-6. doi: 10.1126/science.1209038.

  PMID: 22116877 BACKGROUND

• Aral K, Aral CA, Kapila Y. The role of caspase-8, caspase-9, and apoptosis inducing factor in periodontal disease. J Periodontol. 2019 Mar;90(3):288-294. doi: 10.1002/JPER.17-0716. Epub 2018 Oct 26.

  PMID: 30311940 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Residual gingival crevicular fluid (GCF) samples and complementary DNA (cDNA) samples synthesized from extracted RNA will be retained as backup specimens. Retained GCF samples will be used only if repeat ELISA analysis is required due to technical issues, such as assay failure, insufficient sample volume, or inconclusive results. Retained cDNA samples will be used only if repeat RT-qPCR analysis is required for the same reasons. No genomic DNA extraction will be performed on any retained specimen, and retained specimens will not be used to extract or analyze genomic DNA. All samples will be stored at -80°C and will be used exclusively for quality control and re-analysis purposes related to this study.

MeSH Terms

Conditions

Periodontitis; Gingivitis

Condition Hierarchy (Ancestors)

Periodontal Diseases; Mouth Diseases; Stomatognathic Diseases; Infections; Gingival Diseases

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: August 3, 2026
• First Posted: August 7, 2026
• Study Start: September 15, 2025
• Primary Completion: February 15, 2026
• Study Completion: February 15, 2026
• Last Updated: August 7, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 6 months and ending 24 months following article publication
• Access Criteria: Data will be made available to researchers who provide a methodologically sound proposal, subject to approval by the corresponding author, for the purpose of achieving the aims outlined in the approved proposal.

Locations

TU (1)