- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica NCT07601685
MERC Proteins in Saliva and GCF in Periodontal Disease (ELISA Study) (EKNMERC-GCF-SL)
Expression of Mitochondria-Endoplasmic Reticulum Contact Proteins in Saliva and Gingival Crevicular Fluid in Patients With Periodontal Disease: ELISA and Calcium Analysis
This observational cross-sectional study investigates the levels of mitochondria-endoplasmic reticulum contact site (MERC) proteins in saliva and gingival crevicular fluid (GCF) of individuals with different periodontal conditions. MERCs are specialized regions where mitochondria and the endoplasmic reticulum physically connect, and they play important roles in calcium signaling, oxidative stress regulation, and cell death (apoptosis). Disruption of these contact sites has been linked to inflammatory diseases, including periodontal disease.
The study includes 48 systemically healthy, non-smoking adults divided into three groups: periodontally healthy (n=16), gingivitis (n=16), and Stage III Grade B periodontitis (n=16). Five MERC-associated proteins (VAPB, PTPIP51, IP3R, GRP75, and VDAC) are measured in GCF and saliva samples using ELISA. Additionally, caspase-3 (a marker of apoptosis), reactive oxygen species (a marker of oxidative stress), and calcium levels are measured to explore relationships between MERC proteins and key cellular processes involved in periodontal tissue destruction.
The purpose of this study is to determine whether MERC protein levels differ across periodontal conditions and to evaluate their associations with clinical periodontal parameters, oxidative stress, calcium metabolism, and apoptosis.
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
Mitochondria-endoplasmic reticulum contact sites (MERCs) are specialized structural domains that physically link mitochondria and the endoplasmic reticulum. These contact sites are enriched with functional proteins that coordinate calcium transfer between the two organelles, regulate lipid metabolism, modulate oxidative stress responses, and control apoptotic signaling pathways. Key MERC-associated proteins include VAPB (vesicle-associated membrane protein-associated protein B), PTPIP51 (protein tyrosine phosphatase-interacting protein 51), IP3R (inositol 1,4,5-trisphosphate receptor), GRP75 (glucose-regulated protein 75), and VDAC (voltage-dependent anion channel). The IP3R-GRP75-VDAC complex facilitates calcium transfer from the ER to mitochondria, while the VAPB-PTPIP51 complex modulates this process and influences ATP production and autophagy. Disruption of MERC homeostasis has been implicated in neurodegenerative diseases, metabolic disorders, and periodontal disease. Periodontal disease is a chronic inflammatory condition driven by microbial dental plaque, leading to destruction of periodontal tissues and alveolar bone. Previous studies demonstrated dysregulation of MERC-related gene expression (MFN1, IP3R, GRP75, PINK1, SIGMAR1) in human gingival fibroblasts exposed to Porphyromonas gingivalis and Fusobacterium nucleatum.
The present study measures the concentrations and total amounts of five MERC proteins-VAPB, PTPIP51, IP3R, GRP75, and VDAC-together with caspase-3 (an apoptosis marker), reactive oxygen species (ROS, an oxidative stress marker), and calcium levels in gingival crevicular fluid (GCF) and unstimulated whole saliva obtained from systemically healthy, non-smoking participants. Participants are classified into three groups according to the 2017 World Workshop classification: periodontally healthy (n=16), gingivitis (n=16), and Stage III Grade B periodontitis (n=16), with equal sex distribution (8 males and 8 females per group). GCF samples are collected from three single-rooted teeth per participant using standardized paper strips (Periopaper), with absorbed volume measured using a Periotron 8000. Saliva samples are collected using the passive drooling method. Biomarker levels are quantified using commercially available ELISA kits. Clinical periodontal parameters recorded include Plaque Index (PI), Gingival Index (GI), Probing Depth (PD), Bleeding on Probing (BOP%), and Clinical Attachment Level (CAL). Correlations between biomarker levels and clinical parameters are analyzed. Receiver operating characteristic (ROC) curve analysis is performed to evaluate the diagnostic potential of the biomarkers.
Tipo di studio
Iscrizione (Effettivo)
Contatti e Sedi
Luoghi di studio
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Malatya
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Malatya, Malatya, Turchia (Türkiye), 44210
- Inönü University Faculty of Dentistry, Department of Periodontology
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
- Adulto
- Adulto più anziano
Accetta volontari sani
Metodo di campionamento
Popolazione di studio
Descrizione
Inclusion Criteria:
- Systemically healthy individuals aged 18-65 years
- Non-smokers or smoking cessation more than 5 years ago
- Healthy group: No history of periodontal disease, ≥20 teeth, probing depth (PD) ≤3 mm at all sites, bleeding on probing (BOP) <10%, radiographic CEJ-to-alveolar bone crest distance ≤3 mm in ≥95% of teeth
- Gingivitis group: No history of periodontal disease, ≥20 teeth, PD ≤3 mm at all sites, BOP ≥30%, radiographic CEJ-to-alveolar bone crest distance ≤3 mm in ≥95% of teeth
- Periodontitis group: ≥15 teeth, >30% of teeth affected by periodontal disease, PD ≥6 mm, clinical attachment loss (CAL) ≥5 mm, vertical bone loss ≥3 mm, Class II or III furcation involvement, radiographic alveolar bone loss extending to the middle third or beyond (≥33%), bone loss-to-age ratio between 0.25 and 1.00
Exclusion Criteria:
- Periodontal treatment or antibiotic use within the past 6 months
- Fewer than 20 teeth (excluding third molars)
- Presence of any systemic disease
- Current smoking or cessation within the past 5 years
- Use of immunosuppressive medication
- Alcohol consumption
- Regular medication use
- Pregnancy or lactation
- Need for antibiotic prophylaxis prior to dental procedures
- Prosthetic restorations on the teeth selected for sampling
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
Coorti e interventi
Gruppo / Coorte |
Intervento / Trattamento |
|---|---|
|
Periodontally Healthy
Systemically healthy, non-smoking individuals with no history of periodontal disease.
Inclusion criteria: ≥20 teeth, probing depth (PD) ≤3 mm at all sites, bleeding on probing (BOP) <10%, and radiographic CEJ-to-alveolar bone crest distance ≤3 mm in ≥95% of teeth.
n=16 (8 females, 8 males).
|
Levels of MERC-associated proteins (VAPB, PTPIP51, IP3R, GRP75, VDAC), caspase-3, reactive oxygen species, and calcium were measured in gingival crevicular fluid and unstimulated whole saliva samples using commercially available ELISA kits.
Absorbance was read at 450 nm.
No therapeutic intervention was applied; this is an observational biomarker measurement study.
Calcium levels were measured in gingival crevicular fluid and unstimulated whole saliva samples using a commercially available ELISA kit (ELK Biotechnology, China).
Concentrations were expressed as μmol/mL and total amounts as μmol/30s.
Analytical range: 0.15-40 μmol/mL.
No therapeutic intervention was applied.
|
|
Gingivitis
Systemically healthy, non-smoking individuals with gingival inflammation but no attachment loss.
Inclusion criteria: ≥20 teeth, PD ≤3 mm at all sites, BOP ≥30%, and radiographic CEJ-to-alveolar bone crest distance ≤3 mm in ≥95% of teeth.
n=16 (8 females, 8 males).
|
Levels of MERC-associated proteins (VAPB, PTPIP51, IP3R, GRP75, VDAC), caspase-3, reactive oxygen species, and calcium were measured in gingival crevicular fluid and unstimulated whole saliva samples using commercially available ELISA kits.
Absorbance was read at 450 nm.
No therapeutic intervention was applied; this is an observational biomarker measurement study.
Calcium levels were measured in gingival crevicular fluid and unstimulated whole saliva samples using a commercially available ELISA kit (ELK Biotechnology, China).
Concentrations were expressed as μmol/mL and total amounts as μmol/30s.
Analytical range: 0.15-40 μmol/mL.
No therapeutic intervention was applied.
|
|
Stage III Grade B Periodontitis
Systemically healthy, non-smoking individuals with Stage III Grade B periodontitis.
Inclusion criteria: ≥15 teeth, >30% of teeth affected, PD ≥6 mm, CAL ≥5 mm, vertical bone loss ≥3 mm, Class II/III furcation involvement, radiographic bone loss extending to the middle third or beyond (≥33%), and bone loss-to-age ratio between 0.25 and 1.00.
n=16 (8 females, 8 males).
|
Levels of MERC-associated proteins (VAPB, PTPIP51, IP3R, GRP75, VDAC), caspase-3, reactive oxygen species, and calcium were measured in gingival crevicular fluid and unstimulated whole saliva samples using commercially available ELISA kits.
Absorbance was read at 450 nm.
No therapeutic intervention was applied; this is an observational biomarker measurement study.
Calcium levels were measured in gingival crevicular fluid and unstimulated whole saliva samples using a commercially available ELISA kit (ELK Biotechnology, China).
Concentrations were expressed as μmol/mL and total amounts as μmol/30s.
Analytical range: 0.15-40 μmol/mL.
No therapeutic intervention was applied.
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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GCF VAPB Levels
Lasso di tempo: At baseline (single visit)
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Concentrations and total amounts of VAPB in gingival crevicular fluid measured by ELISA.
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At baseline (single visit)
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Salivary VAPB Levels
Lasso di tempo: At baseline (single visit)
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Concentrations of VAPB (pg/mL) in unstimulated whole saliva measured by ELISA.
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At baseline (single visit)
|
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GCF PTPIP51 Levels
Lasso di tempo: At baseline (single visit)
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Concentrations and total amounts of PTPIP51 in gingival crevicular fluid measured by ELISA.
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At baseline (single visit)
|
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Salivary PTPIP51 Levels
Lasso di tempo: At baseline (single visit)
|
Concentrations of PTPIP51 (ng/L) in unstimulated whole saliva measured by ELISA.
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At baseline (single visit)
|
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GCF IP3R Levels
Lasso di tempo: At baseline (single visit)
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Concentrations and total amounts of IP3R in gingival crevicular fluid measured by ELISA.
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At baseline (single visit)
|
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Salivary IP3R Levels
Lasso di tempo: At baseline (single visit)
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Concentrations of IP3R (ng/mL) in unstimulated whole saliva measured by ELISA.
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At baseline (single visit)
|
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GCF GRP75 Levels
Lasso di tempo: At baseline (single visit)
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Concentrations and total amounts of GRP75 in gingival crevicular fluid measured by ELISA.
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At baseline (single visit)
|
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Salivary GRP75 Levels
Lasso di tempo: At baseline (single visit)
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Concentrations of GRP75 (ng/mL) in unstimulated whole saliva measured by ELISA.
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At baseline (single visit)
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GCF VDAC Levels
Lasso di tempo: At baseline (single visit)
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Concentrations and total amounts of VDAC in gingival crevicular fluid measured by ELISA.
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At baseline (single visit)
|
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Salivary VDAC Levels
Lasso di tempo: At baseline (single visit)
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Concentrations of VDAC (ng/mL) in unstimulated whole saliva measured by ELISA.
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At baseline (single visit)
|
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GCF Caspase-3 Levels
Lasso di tempo: At baseline (single visit)
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Concentrations and total amounts of caspase-3 (ng/mL) in gingival crevicular fluid measured by ELISA.
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At baseline (single visit)
|
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Salivary Caspase-3 Levels
Lasso di tempo: At baseline (single visit)
|
Concentrations of caspase-3 (ng/mL) in unstimulated whole saliva measured by ELISA.
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At baseline (single visit)
|
|
GCF Reactive Oxygen Species Levels
Lasso di tempo: At baseline (single visit)
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Concentrations and total amounts of reactive oxygen species (ROS) in gingival crevicular fluid measured by ELISA.
|
At baseline (single visit)
|
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Salivary Reactive Oxygen Species Levels
Lasso di tempo: At baseline (single visit)
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Concentrations of reactive oxygen species (ROS) in unstimulated whole saliva measured by ELISA.
|
At baseline (single visit)
|
|
GCF Calcium Levels
Lasso di tempo: At baseline (single visit)
|
Concentrations and total amounts of calcium (µmol/mL) in gingival crevicular fluid measured by ELISA.
|
At baseline (single visit)
|
|
Salivary Calcium Levels
Lasso di tempo: At baseline (single visit)
|
Concentrations of calcium (µmol/mL) in unstimulated whole saliva measured by ELISA.
|
At baseline (single visit)
|
|
Plaque Index
Lasso di tempo: At baseline (single visit)
|
Plaque Index (PI) recorded at sampling sites.
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At baseline (single visit)
|
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Gingival Index
Lasso di tempo: At baseline (single visit)
|
Gingival Index (GI) recorded at sampling sites.
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At baseline (single visit)
|
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Probing Depth
Lasso di tempo: At baseline (single visit)
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Probing Depth (PD) recorded at sampling sites.
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At baseline (single visit)
|
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Bleeding on Probing
Lasso di tempo: At baseline (single visit)
|
Bleeding on Probing (BOP%) recorded at sampling sites.
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At baseline (single visit)
|
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Clinical Attachment Level
Lasso di tempo: At baseline (single visit)
|
Clinical Attachment Level (CAL) recorded at sampling sites.
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At baseline (single visit)
|
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Gingival Crevicular Fluid Volume
Lasso di tempo: At baseline (single visit)
|
Gingival crevicular fluid (GCF) volume measured at sampling sites.
|
At baseline (single visit)
|
Collaboratori e investigatori
Sponsor
Investigatori
- Cattedra di studio: Cüneyt A Aral, Professor, DDS, PhD, Inonu University
Pubblicazioni e link utili
Pubblicazioni generali
- Papapanou PN, Sanz M, Buduneli N, Dietrich T, Feres M, Fine DH, Flemmig TF, Garcia R, Giannobile WV, Graziani F, Greenwell H, Herrera D, Kao RT, Kebschull M, Kinane DF, Kirkwood KL, Kocher T, Kornman KS, Kumar PS, Loos BG, Machtei E, Meng H, Mombelli A, Needleman I, Offenbacher S, Seymour GJ, Teles R, Tonetti MS. Periodontitis: Consensus report of workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J Clin Periodontol. 2018 Jun;45 Suppl 20:S162-S170. doi: 10.1111/jcpe.12946.
- Chapple ILC, Mealey BL, Van Dyke TE, Bartold PM, Dommisch H, Eickholz P, Geisinger ML, Genco RJ, Glogauer M, Goldstein M, Griffin TJ, Holmstrup P, Johnson GK, Kapila Y, Lang NP, Meyle J, Murakami S, Plemons J, Romito GA, Shapira L, Tatakis DN, Teughels W, Trombelli L, Walter C, Wimmer G, Xenoudi P, Yoshie H. Periodontal health and gingival diseases and conditions on an intact and a reduced periodontium: Consensus report of workgroup 1 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J Periodontol. 2018 Jun;89 Suppl 1:S74-S84. doi: 10.1002/JPER.17-0719.
- Lim D, Dematteis G, Tapella L, Genazzani AA, Cali T, Brini M, Verkhratsky A. Ca2+ handling at the mitochondria-ER contact sites in neurodegeneration. Cell Calcium. 2021 Sep;98:102453. doi: 10.1016/j.ceca.2021.102453. Epub 2021 Aug 5.
- Lee S, Min KT. The Interface Between ER and Mitochondria: Molecular Compositions and Functions. Mol Cells. 2018 Dec 31;41(12):1000-1007. doi: 10.14348/molcells.2018.0438. Epub 2018 Dec 12.
- 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.
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Studia le date principali
Inizio studio (Effettivo)
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Manifestazioni neurologiche
- Malattie della bocca
- Malattie stomatognatiche
- Malattie del cervello
- Malattie del sistema nervoso centrale
- Malattie del sistema nervoso
- Malattie genetiche, congenite
- Infezioni
- Malattie Neurodegenerative
- Malattie gengivali
- Malattie Eredodegenerative, Sistema Nervoso
- Malattie del midollo spinale
- Discinesia
- Malattie cerebellari
- Atassia cerebellare
- Degenerazioni spinocerebellari
- Atassia
- Malattie e anomalie congenite, ereditarie e neonatali
- Parodontite
- Malattie parodontali
- Atassie spinocerebellari
- Gengivite
Altri numeri di identificazione dello studio
- IUCTEC.2024/06
- TDH-2024-3464 (Altro numero di sovvenzione/finanziamento: Inönü University Scientific Research Projects Coordination Office)
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
Informazioni su farmaci e dispositivi, documenti di studio
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Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .
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