- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT07705048
PTPIP51-VAPB Complex in the Periodontal Disease
The Role of PTPIP51-VAPB Complex in the Pathogenesis of Periodontal Disease
Study Overview
Status
Conditions
Detailed Description
Periodontal disease encompasses a spectrum of inflammatory conditions ranging from gingivitis to periodontitis, both of which are driven by the host immune response to periodontopathogenic bacteria such as Porphyromonas gingivalis. Mitochondria-associated endoplasmic reticulum membranes (MAMs) are physical contact sites between the endoplasmic reticulum and mitochondria that regulate calcium exchange, lipid metabolism, and autophagy. The VAPB-PTPIP51 tethering complex is a key molecular determinant of MAM formation, and prior research has shown that alterations in this complex affect autophagosome formation and intracellular calcium homeostasis. However, the role of the VAPB-PTPIP51 complex and autophagy-related protein LC3B in periodontal disease has not been previously characterized.
This study includes two components. First, an observational, cross-sectional investigation was conducted in 60 participants classified into three groups (periodontal health, gingivitis, and periodontitis) according to the 2017 World Workshop classification criteria, based on clinical parameters including plaque index, gingival index, probing depth, clinical attachment level, and bleeding on probing. Gingival tissue biopsies were obtained from participants undergoing clinically indicated periodontal procedures (crown lengthening, gingivectomy, or flap surgery). Tissue samples were analyzed for gene expression (RT-PCR) and protein levels (Western blot) of PTPIP51, VAPB, and LC3B, as well as tissue calcium concentration.
Second, an in vitro experimental component was performed using a commercially available human gingival fibroblast cell line (HGF-1) treated with Porphyromonas gingivalis lipopolysaccharide (LPS) at 5 μg/mL and 10 μg/mL for 24 hours, to evaluate dose-dependent changes in PTPIP51, VAPB, and LC3B gene expression in response to a periodontopathogenic stimulus.
The findings from this study aim to clarify the involvement of the VAPB-PTPIP51 tethering complex and autophagy-related signaling in periodontal tissue destruction, providing mechanistic insight that may inform future therapeutic approaches targeting mitochondria-endoplasmic reticulum communication in periodontal disease.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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Malatya, Turkey (Türkiye), 44100
- Inonu University
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
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
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
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periodontally healthy
periodontally healthy participants
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gingivitis group
patients with gingivitis
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periodontitis
patients with periodontitis
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Gingival PTPIP51, VAPB, and LC3B Gene and Protein Expression
Time Frame: From February to July 2024
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Gene expression (RT-PCR, relative fold change via 2^-ΔΔCT method) and protein expression (Western blot, band intensity normalized to ACTB) of PTPIP51, VAPB, and LC3B were measured and compared in gingival tissue biopsies from participants with periodontal health, gingivitis, and periodontitis
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From February to July 2024
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Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- Kirmizigul OA, Sabanci A, Disli F, Yildiz S, Milward MR, Aral K. Evaluation of the role of mitofusin-1 and mitofusin-2 in periodontal disease. J Periodontol. 2024 Jan;95(1):64-73. doi: 10.1002/JPER.23-0072. Epub 2023 Jul 24.
- Aral K, Milward MR, Cooper PR. Gene expression profiles of mitochondria-endoplasmic reticulum tethering in human gingival fibroblasts in response to periodontal pathogens. Arch Oral Biol. 2021 Aug;128:105173. doi: 10.1016/j.archoralbio.2021.105173. Epub 2021 May 27.
- Gomez-Suaga P, Paillusson S, Stoica R, Noble W, Hanger DP, Miller CCJ. The ER-Mitochondria Tethering Complex VAPB-PTPIP51 Regulates Autophagy. Curr Biol. 2017 Feb 6;27(3):371-385. doi: 10.1016/j.cub.2016.12.038. Epub 2017 Jan 26.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- IU-2024/13
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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