Salivary levels of MPO, MMP-8 and TIMP-1 are associated with gingival inflammation response patterns during experimental gingivitis

Nascimento, Gustavo G.; Bælum, Vibeke; Sorsa, Timo; Tervahartiala, Taina; Skottrup, Peter Durand; López, Rodrigo

doi:10.1016/j.cyto.2018.12.002

Cited by 31 publications

(33 citation statements)

References 22 publications

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“…Nascimento's study also showed MMP-8 signi cantly increased during the process of experimental gingivitis [23], all these data indicated that MMP-8 increased with the development of gingival in ammation and kept stable in the subsequent stage of disease.…”

Section: Discussionmentioning

confidence: 81%

Evaluation of Salivary Biomarkers for the Diagnosis of Periodontitis

Zhang

Kang

Xue

et al. 2020

Preprint

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Background: To investigate the diagnostic potential of salivary biomarkers and built a prediction panel for diagnosing periodontal disease. Methods: In a cross-sectional study, a total of 85 participants were enrolled in the study and divided into healthy, gingivitis and periodontitis groups based on their periodontal examine results, a full mouth periodontal examination were received and unstimulated saliva were collected. Salivary IL-1β, MMP-8, ICTP and Pg were assessed and their potential of diagnosing periodontal disease were analyzed, the combinational prediction panels of periodontal disease were evaluated. Results: The periodontitis group showed significantly higher level of IL-1β, MMP-8, ICTP and Pg compared to healthy group and higher level of IL-1β, ICTP and Pg compared to gingivitis group, the gingivitis group showed higher level of IL-1β, MMP-8 and Pg compared to healthy group. As a single marker, IL-1β showed the best diagnostic value of four markers and exhibited an AUC value of 0.88 with 94% sensitivity and 71% specificity to discriminate periodontitis from healthy subjects, an AUC value of 0.81 with 82% sensitivity and 76% specificity to discriminate gingivitis from healthy subjects and an AUC value of 0.67 with 69% sensitivity and 64% specificity to discriminate periodontitis from gingivitis subjects. The combination of IL-1, ICTP and Pg exhibited the highest value to discriminate periodontitis from healthy (AUC=0.94) and gingivitis (AUC=0.78) subjects, the combination of IL-1 and MMP-8 exhibited the best value to discriminate gingivitis from healthy subjects (AUC=0.85). Conclusions: Salivary IL-1β, MMP-8, ICTP and Pg showed discriminate efficiency for diagnosing periodontal disease, the combination of IL-1, ICTP and Pg can be used to discriminate periodontitis from healthy and gingivitis subjects and the combination of IL-1 and MMP-8 can be used to discriminate gingivitis from healthy subjects.

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Section: Discussionmentioning

confidence: 81%

Evaluation of Salivary Biomarkers for the Diagnosis of Periodontitis

Zhang

Kang

Xue

et al. 2020

Preprint

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“…Further investigation by Nascimento et al . (37) measured the salivary levels of MMP‐8, myeloperoxidase, and TIMP‐1, and suggested that the faster responders had greater neutrophil involvement. A larger number of participants in future studies may help with identification of these kinds of groups, using the methods presented in this study.…”

Section: Discussionmentioning

confidence: 99%

Predicted salivary human protease activity in experimental gingivitis revealed by endoProteo‐FASP approach

Mulkern

Hewitt

Parker

et al. 2020

European J Oral Sciences

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Gingivitis is a highly prevalent oral condition that can be studied in humans via the 21‐d experimental gingivitis model, which allows for investigations into the induction and resolution of gingivitis. In this study, we used the autolysis of saliva as a source of peptides to predict the activity of human proteases in saliva during induction and resolution of inflammation. Healthy volunteers, with no remarkable oral or systemic conditions, were recruited into the study and stimulated saliva samples were collected at days 0, 21, and 35 of experimental gingivitis. Plaque and gingival indices were recorded to ensure clinical induction and resolution. Saliva was auto‐digested at 37°C for 18 h before identification of peptides by mass spectrometry. Protease prediction was carried out using Proteasix in silico with the identified peptides. A comparison of day 0 to days 21 and 35 showed changes in predicted protease activity. Correlation network analysis revealed that at day 21 the proteases became less connected and showed a potential for a dysregulated system; by day 35 the connectivity was returning towards similar conditions at day 0. This study demonstrates that changes in predicted proteases are apparent even in saliva collected from donors experiencing inflammation around three teeth.

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“…Commercially available ELISA kits were used to measure levels of TIMP‐1 (Biotrak ELISA systems, Amersham Biosciences UK Ltd, Buckinghamshire, UK), MPO (Immundiagnostik AG, Bensheim, Germany), and PMN elastase (Bender MedSystems mbH, Vienna, Austria) in saliva according to the manufacturer's guidelines as described before …”

Section: Methodsmentioning

confidence: 99%

Label‐Free Quantitative Proteomics versus Antibody‐Based Assays to Measure Neutrophil‐Derived Enzymes in Saliva

Silbereisen

Alassiri

Bao

et al. 2020

Proteomics Clinical Apps

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Purpose: This study aims to validate label-free quantitative proteomics (LFQ) against antibody-based methods for quantifying established periodontal disease biomarkers in saliva. Experimental Design: In an experimental gingivitis model, healthy volunteers (n = 10) provide saliva at baseline (d0), during the induction (d7, d14, d21) and resolution (d35) of gingival inflammation (total n = 50). Biomarker levels are analyzed by LFQ and time-resolved immunofluorometric assay (IFMA) or enzyme-linked immunosorbent assay (ELISA). Molecular matrix metalloproteinase (MMP)-8 forms are assessed by Western blot (WB) analysis. Results: LFQ detects significantly (p < 0.05) elevated MMP-8 (d21vsd7, d35vsd7) and tissue inhibitor of matrix metalloproteinases (TIMP)-1 (d35vsd7). Latent MMP-8 (70-80 kDa) is present (d0-d35), but not active MMP-8 (50-60 kDa). LFQ and immunoassay data significantly correlate for MMP-8 (r = 0.36), myeloperoxidase (r = 0.39), polymorphonuclear leukocyte elastase (r = 0.33), and TIMP-1 (r = −0.24).Conclusion and Clinical Relevance: LFQ can quantify enzyme levels in saliva, however lacks the ability to measure enzymatic activity. WB analysis reveals that MMP-8 may not be activated during induction of gingival inflammation. Significant but weak correlations between IFMA or ELISA and LFQ suggest a limited capacity of available antibodies to reliably quantify salivary biomarkers for periodontal diseases. Novel "anti-peptide" antibodies designed by newer targeted mass spectrometry-based approaches can help to overcome these drawbacks.

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Salivary levels of MPO, MMP-8 and TIMP-1 are associated with gingival inflammation response patterns during experimental gingivitis

Cited by 31 publications

References 22 publications

Evaluation of Salivary Biomarkers for the Diagnosis of Periodontitis

Evaluation of Salivary Biomarkers for the Diagnosis of Periodontitis

Predicted salivary human protease activity in experimental gingivitis revealed by endoProteo‐FASP approach

Label‐Free Quantitative Proteomics versus Antibody‐Based Assays to Measure Neutrophil‐Derived Enzymes in Saliva

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