Analysis of HIF-1α, MDA, and GPX4 in Peri-Implant Crevicular Fluid

NCT06863116 | Completed

• 1 other identifier: 23-4.1T/14
• Study Type: observational
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

Peri-implant diseases, such as peri-implant mucositis and peri-implantitis, are inflammatory conditions that affect the tissues surrounding dental implants. If untreated, these diseases can lead to bone loss and implant failure. This study investigates whether low oxygen levels (hypoxia) in the peri-implant environment influence ferroptosis, a type of cell death associated with oxidative stress. The research focuses on three key biomarkers: hypoxia-inducible factor-1 alpha (HIF-1α), glutathione peroxidase-4 (GPX-4), and malondialdehyde (MDA). A total of 45 participants with 62 dental implants were included in the study. They were divided into three groups: peri-implant health, peri-implant mucositis, and peri-implantitis. Peri-implant crevicular fluid (PICF) samples were collected, and the levels of HIF-1α, GPX-4, and MDA were measured using laboratory tests. The study aims to determine whether hypoxia affects ferroptosis-related pathways by altering GPX-4 and MDA levels. Understanding these mechanisms could provide new insights into peri-implant disease progression and help develop improved treatment strategies.

Conditions

Peri-Implantitis and Peri-implant Mucositis; Hypoxia; Ferroptosis

Keywords

Peri-Implantitis; Peri-implant mucositis; Hypoxia; Ferroptosis; Lipid Peroxidation

Outcome Measures

Primary Outcomes (1)

• HIF-1α, GPX-4, and MDA Levels in Peri-Implant Crevicular Fluid

  Measurement of hypoxia-inducible factor-1 alpha (HIF-1α), glutathione peroxidase-4 (GPX-4), and malondialdehyde (MDA) levels in peri-implant crevicular fluid using enzyme-linked immunosorbent assay (ELISA) to assess their association with peri-implant health, mucositis, and peri-implantitis.

  Cross-sectional measurement at a single time point

Study Arms (3)

Peri-Implant Health

Participants with no clinical signs of peri-implant disease. These individuals exhibit healthy peri-implant soft tissues with no bleeding on probing (BOP), probing depth (PD) ≤ 4 mm, and no radiographic bone loss.

Peri-Implant Mucositis

Participants diagnosed with peri-implant mucositis, characterized by bleeding on probing (BOP) and/or signs of inflammation (redness, swelling), but without radiographic bone loss beyond early remodeling.

Peri-Implantitis

Participants diagnosed with peri-implantitis, defined by increased probing depth (PD \> 5 mm), bleeding on probing (BOP) or suppuration, and radiographic evidence of bone loss beyond initial remodeling.

Eligibility Criteria

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

Study Population

This study included individuals with at least one dental implant, recruited from the Department of Periodontology, Ege University, Faculty of Dentistry. Participants were selected based on specific eligibility criteria, ensuring that they had an implant functioning for at least one year and no history of systemic diseases or recent periodontal treatments. The study population consisted of individuals diagnosed with peri-implant health, peri-implant mucositis, or peri-implantitis, classified according to clinical and radiographic findings. All participants provided informed consent before sample collection.

You may qualify if:

• Participants must have at least one dental implant functioning for a minimum of one year.
• No history of systemic diseases.
• No periodontal treatments (surgical or non-surgical) in the past six months.
• No use of antibiotics or other medications within the past six months.

You may not qualify if:

• Systemic diseases, including but not limited to:
• Diabetes mellitus Rheumatoid arthritis Cardiovascular disorders Immunological disorders Mucocutaneous diseases Contagious or communicable diseases
• Medication use, including:
• Immunosuppressants Steroids Non-steroidal anti-inflammatory drugs (NSAIDs) Antiepileptics Calcium channel blockers Beta-blockers Anticoagulants Hormonal contraceptives Nutritional supplements
• Pregnant or lactating women.
• Use of orthodontic appliances or removable partial dentures.
• Poorly maintained implant-supported prostheses that may interfere with peri-implant crevicular fluid collection.

Sponsors & Collaborators

• Ege University: lead

Study Sites (1)

Ege University, Faculty of Dentistry, Department of Periodontology

Izmir, 35040, Turkey (Türkiye)

Location

Related Publications (6)

• Gao X, Hu W, Qian D, Bai X, He H, Li L, Sun S. The Mechanisms of Ferroptosis Under Hypoxia. Cell Mol Neurobiol. 2023 Oct;43(7):3329-3341. doi: 10.1007/s10571-023-01388-8. Epub 2023 Jul 17.

  PMID: 37458878 RESULT

• Hsieh CH, Lin YJ, Chen WL, Huang YC, Chang CW, Cheng FC, Liu RS, Shyu WC. HIF-1alpha triggers long-lasting glutamate excitotoxicity via system xc- in cerebral ischaemia-reperfusion. J Pathol. 2017 Feb;241(3):337-349. doi: 10.1002/path.4838. Epub 2016 Dec 29.

  PMID: 27801527 RESULT

• Fan Y, Ma L, Fang X, Du S, Mauck J, Loor JJ, Sun X, Jia H, Xu C, Xu Q. Role of hypoxia-inducible-factor-1alpha (HIF-1alpha) in ferroptosis of adipose tissue during ketosis. J Dairy Sci. 2024 Dec;107(12):10611-10627. doi: 10.3168/jds.2024-24822. Epub 2024 Jul 26.

  PMID: 39067746 RESULT

• Afacan B, Ozturk VO, Pasali C, Bozkurt E, Kose T, Emingil G. Gingival crevicular fluid and salivary HIF-1alpha, VEGF, and TNF-alpha levels in periodontal health and disease. J Periodontol. 2019 Jul;90(7):788-797. doi: 10.1002/JPER.18-0412. Epub 2018 Dec 11.

  PMID: 30536725 RESULT

• Xing L, Dong W, Chen Y, Dai W, Xiao X, Liu Z, Zhang X, Bai D, Xu H. Fibroblast ferroptosis is involved in periodontitis-induced tissue damage and bone loss. Int Immunopharmacol. 2023 Jan;114:109607. doi: 10.1016/j.intimp.2022.109607. Epub 2022 Dec 22.

  PMID: 36700777 RESULT

• Qiao S, Li B, Cai Q, Li Z, Yin Z, He J, Li Y, Meng W. Involvement of ferroptosis in Porphyromonas gingivalis lipopolysaccharide-stimulated periodontitis in vitro and in vivo. Oral Dis. 2023 Nov;29(8):3571-3582. doi: 10.1111/odi.14292. Epub 2022 Jul 12.

  PMID: 35765229 RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

Peri-implant crevicular fluid (PICF) samples were collected from study participants for biomarker analysis. No DNA extraction is planned from these samples.

MeSH Terms

Conditions

Peri-Implantitis; Hypoxia

Condition Hierarchy (Ancestors)

Periodontal Diseases; Mouth Diseases; Stomatognathic Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

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

Study Record Dates

• First Submitted: March 3, 2025
• First Posted: March 7, 2025
• Study Start: May 15, 2023
• Primary Completion: May 15, 2024
• Study Completion: July 16, 2024
• Last Updated: March 7, 2025

Record last verified: 2025-03

Locations

TU (1)