Publications by authors named "Taina Tervahartiala"

158 Publications

Evaluation of active matrix metalloproteinase-8 (aMMP-8) chair-side test as a diagnostic biomarker in the staging of periodontal diseases.

Arch Oral Biol 2021 Apr 20;124:104955. Epub 2021 Jan 20.

Department of Oral and Maxillofacial Diseases, University of Helsinki, Helsinki University Hospital, Institute of Dentistry, Helsinki, Finland.

Objective: There is a need for a reliable complementary diagnostic tool that ideally helps to screen, differentiate sites, activities of and predict future periodontal tissue destruction. The purpose of this cross-sectional study was to investigate the screening and prevention potential of the chair-side/point-of-care (PoC) diagnostic test of salivary active matrix metalloproteinase-8 (aMMP-8) levels at different stages of periodontal disease and periodontal health.

Material & Methods: 80 individuals were included in this study; 18 with periodontitis stage 3 (P-Stage III), 19 with periodontitis stage-4 (P-Stage IV), 21 with gingivitis, and 22 with clinically healthy periodontium (H). The aMMP-8 levels in GCF and saliva were analyzed by chairside point-of-care aMMP-8 lateral flow immunotest and also by a time-resolved immunofluorescence assay (IFMA).

Results: The sensitivity of the chair-side/PoC test was 83.9 % while specificity was 79.2 %. The aMMP-8 IFMA levels in GCF were significantly higher in P-Stage IV group than P-Stage III, gingivitis and healthy groups (p = 0.01, p = 0.001, p = 0.00, respectively). Moreover, P-Stage III and gingivitis groups had significantly higher aMMP-8 IFMA levels than the healthy group (p < 0.05).

Conclusion: The aMMP-8 chair-side test showed promising results in its ability to recognize and predict the inflammatory status even at the very initial/early stages. aMMP-8 chair-side test could be a valuable adjunctive diagnostic and preventive tool to conventional clinical methods in detecting periodontal disease.
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http://dx.doi.org/10.1016/j.archoralbio.2020.104955DOI Listing
April 2021

Regulation of matrix metalloproteinases-8, -9 and endogenous tissue inhibitor-1 in oral biofluids during pregnancy and postpartum.

Arch Oral Biol 2021 Apr 23;124:105065. Epub 2021 Jan 23.

Department of Periodontology, School of Dentistry, Ege University, İzmir, Turkey.

Objective: During pregnancy, mothers undergoe considerable physiological changes affecting the whole body including periodontal tissues. Susceptibility to gingival inflammation during pregnancy could be mediated by modulation of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). Therefore, the aim of this study was to investigate salivary and gingival crevicular fluid (GCF) levels of MMPs and TIMPs during the second and third trimester of pregnancy and postpartum.

Design: Saliva and GCF samples were collected from 96 pregnant women (PW) before and after giving birth. The sixty matched non-pregnant women (N-PW) were recruited as a control group and full-mouth periodontal examination was performed. The levels of MMP-8, MMP-9 and TIMP-1 were determined by immunofluorometric and enzyme-linked immunosorbent assays.

Results: The PW group exhibited significantly higher levels of MMP-8 and MMP-9 in their saliva than the N-PW group while corresponding salivary TIMP-1 levels were significantly lower in NPW compared to the postpartum stage. This resulted in significantly higher MMP-8/TIMP-1 and MMP-9/TIMP-1ratio in the saliva from PW before and after birth than in that from N-PW. MMP-8, MMP-9 and TIMP-1 levels were higher in GCF from PW and postpartum than in that from N-PW.

Conclusions: MMP-8 and MMP-9 levels in saliva and GCF reflect inflammatory burden during pregnancy. They could be used for monitoring the inflammatory state of gingival tissues during pregnancy.
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http://dx.doi.org/10.1016/j.archoralbio.2021.105065DOI Listing
April 2021

Lingonberry polyphenols: Potential SARS-CoV-2 inhibitors as nutraceutical tools?

Physiol Rep 2021 02;9(3):e14741

Faculty of Medicine, Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, Finland.

Proposed pathway of the effect of lingonberry polyphenols on oral microbial (viral) load reduction and consequent beneficial local and systemic (respiratory tract) anti-inflammatory and antimicrobial/antiviral effects.
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http://dx.doi.org/10.14814/phy2.14741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851427PMC
February 2021

Active matrix metalloproteinase-8 and interleukin-6 detect periodontal degeneration caused by radiotherapy of head and neck cancer: a pilot study.

Expert Rev Proteomics 2020 10 7;17(10):777-784. Epub 2021 Jan 7.

Department of Oral and Maxillofacial Diseases, University of Helsinki, Helsinki University Hospital , Helsinki, Finland.

: This cohort study investigated the role of the active matrix metalloproteinase-8 (aMMP-8) and interleukin-6 (IL-6) as oral fluid biomarkers for monitoring the periodontal degeneration occurring in head and neck cancer (HNC) patients treated by radiotherapy. : Eleven patients, aged 28-74, diagnosed with HNC were included in the study. Complete periodontal and oral examinations were performed pre-radiotherapy and 1 month after radiotherapy. Mouthrinse samples (pre-radiotherapy, after 6 weeks of radiotherapy and 1 month after radiotherapy) were assayed by aMMP-8 point-of-care-kit (PerioSafe®/ORALyzer®) for aMMP-8 and ELISA for IL-6. : HNC radiotherapy had a deteriorating impact on the periodontium and a significant impact on periodontal biomarkers aMMP-8 and IL-6 and increased their levels in mouthrinse. Clinical-attachment-loss (CAL) (site of greatest loss: mean = 1.7 mm, range = 1-3 mm) corresponding to rapid progression of periodontitis. There was a positive repeated measures correlation (rmcorr = 0.667) between the aMMP-8 and IL-6 levels. : Elevated aMMP-8 levels were observed 1 month after radiotherapy among some HNC patients suggesting a prolonged increased susceptibility to further periodontal tissue destruction. Currently available aMMP-8 point-of-care testing could be useful to monitor and assess quantitatively online and real-time the risk of deterioration of periodontal health during HNC radiotherapy.
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http://dx.doi.org/10.1080/14789450.2020.1858056DOI Listing
October 2020

Low association between bleeding on probing propensity and the salivary aMMP-8 levels in adolescents with gingivitis and stage I periodontitis.

J Periodontal Res 2020 Dec 11. Epub 2020 Dec 11.

Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background And Objective: Bleeding on probing (BOP) is a widely accepted measure used in periodontal diagnostics. Previous studies suggest that several factors can affect BOP propensity. The aim of this study was to investigate the relative impact of different local and modifying factors on BOP levels.

Materials And Methods: The oral health of five hundred and forty-four adolescents (two birth cohorts) aged 15-17 years living in Kotka, Finland, was examined including periodontal probing depth, visible plaque index, root calculus, and BOP. Whole saliva samples were collected and measured for active matrix metalloproteinase-8 (aMMP-8) by time-resolved immunofluorometric assay (IFMA).

Results: Bacterial plaque/calculus accumulation (oral hygiene) had a major influence on BOP levels. The relative impact was several times greater compared with the extent of periodontal pocketing, aMMP-8 levels, smoking, toothbrushing, or gender. Furthermore, BOP levels were significantly elevated among adolescents with poor oral hygiene than good oral hygiene even if adjusted for the extent of periodontal pocketing (P < .001). BOP levels could be low even if several ≥ 4 mm deep periodontal pockets existed. The difference in the extent of periodontal pocketing was not significant between the two birth cohorts of adolescents (P = .731).

Conclusions: BOP levels can be regarded as an important indicator of the extent of bacterial challenge and its adverse effects on the gingival inflammation. However, the level of oral hygiene may mask the association between the extent of gingival bleeding and the severity of the periodontal inflammatory condition. Thus, relying on BOP levels (below 10% or 20%) may provide insufficient information about the periodontal treatment need of an adolescent depending on his/her level of oral hygiene. Yet, more research is needed to confirm the results, also in adult populations.
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http://dx.doi.org/10.1111/jre.12817DOI Listing
December 2020

Prediabetes/diabetes screening strategy at the periodontal clinic.

Clin Exp Dent Res 2021 Feb 10;7(1):85-92. Epub 2020 Dec 10.

Department of Preventive Dentistry, Periodontology and Implant Biology, Dental School, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Objective: The aim of the study was to propose an efficient chairside clinical strategy for the identification of undiagnosed hyperglycaemia in periodontal clinics.

Material And Methods: Α chairside system was used for assessment of glycated hemoglobin 1c (HbA1c) and active Matrix Metalloproteinase-8 levels (aMMP-8) were analyzed by immunotest in patients (n = 150) who fulfilled the criteria for screening of the Centers for Disease Control and Prevention. Full-mouth periodontal parameters were assessed and various data such as Body Mass Index (BMI), smoking and education were recorded.

Results: Thirty-one patients out of 150 tested were found with unknown hyperglycaemia (20.7%). Regarding sex, education, parent with diabetes, normal BMI, smoking, age ≥45 years and prior testing for diabetes, no differences were observed between subjects displaying HbA1c < 5.7 and ≥5.7% (Pearson's Chi-square test, p > .05). Subgroups differed regarding BMI (kg/m ), tooth count, percentages of 4 and 5 mm pockets (Mann-Whitney and z-test, p < .05). The diagnostic performance for HbA1c ≥5.7 was tested by Receiving Operator Characteristic curves and Areas Under the Curve (AUC) for the following: age ≥ 45 years and BMI (AUC 0.651, p = .010), the above and aMMP-8 (AUC 0.660, p = .006), age ≥ 45 years, BMI and Stage of Periodontitis (AUC 0.711, p < .001) and age ≥ 45 years, BMI, aMMP-8 and stage of periodontitis (AUC 0.713, p < .001).

Conclusions: Findings of the study suggest that the combination of stage of periodontitis, increasing age, BMI and aMMP-8, without chairside HbA1c assessment appears to be a viable screening strategy for referring dental patients for testing for prediabetes/diabetes.
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http://dx.doi.org/10.1002/cre2.338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853879PMC
February 2021

Periodontal disease and targeted prevention using aMMP-8 point-of-care oral fluid analytics in the COVID-19 era.

Med Hypotheses 2020 Nov 16;144:110276. Epub 2020 Sep 16.

Department of Oral and Maxillofacial Diseases, Helsinki University and University Hospital, Helsinki, Finland; Department of Oral Diseases, Karolinska Institutet, Huddinge, Sweden.

Periodontal disease is a chronic multifactorial infectious and inflammatory disease associated with several chronic systemic diseases, such as diabetes, cardiovascular diseases (CVD), chronic obstructive pulmonary disease, hypertension, Alzheimer's disease and so on. These same systemic diseases have been associated with severe COVID-19 infections. Several recent studies have suggested hypotheses for the potential association between periodontal disease and severe COVID-19. Periodontal disease is also one of the most prevalent diseases globally. All this supports the importance of good oral health, also in the COVID-19 era. Thus, new strategies and approaches to identify patients at risk of periodontal disease could be beneficial to enhance secondary prevention, especially if targeted to COVID-19 risk groups. Diagnostic biomarkers for periodontal disease have been researched extensively. Potential biomarkers in oral fluid with currently available rapid non-invasive point-of-care technology, such as aMMP-8, could help to extend screening and identification of patients at risk for periodontal disease also to situations and places where professional dental expertise and equipment are limited or unavailable. i.e., nursing and care homes, and rural and distant places. The oral fluid point-of-care technologies could also be useful in the hands of medical professionals (diabetes, CVD, etc.) to identify patients at risk for undiagnosed periodontal disease and to refer them to a dentist for examination and evaluation. Finally, if there is a causality between periodontal disease and severe COVID-19 infections, these point-of-care oral fluid biomarker technologies could possibly also help in the assessment of the risk of deterioration and complications.
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http://dx.doi.org/10.1016/j.mehy.2020.110276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492808PMC
November 2020

Adjunctive Antiseptic Irrigation of Periodontal Pockets: Effects on Microbial and Cytokine Profiles.

Dent J (Basel) 2020 Nov 2;8(4). Epub 2020 Nov 2.

Department of Dental Medicine, Division of Periodontology, Karolinska Institutet, 14152 Huddinge, Sweden.

To evaluate the effect of adjunctive antiseptic irrigation of periodontal pockets on microbial and cytokine profiles. Fifty-nine patients with severe periodontitis were allocated to one of three groups for scaling and root planing facilitated with different adjunctive antiseptics: 1% polyhexamethyleneguanidine phosphate (PHMG-P) (n = 19), 0.2% chlorhexidine (CHX) (n = 21) or distilled water (n = 19). Gingival crevicular fluid and subgingival bacterial samples were collected at baseline, and at 2 weeks, and 1 and 4 months. The levels of interleukin (IL)-1β, IL-8, IL-10, and IL-17A, matrix metalloproteinase (MMP)-8, , , , , and were determined. There were no intergroup differences in cytokine concentrations and bacterial counts at any follow-up, however, varying patterns were observed. In the PHMG-P and water groups IL-1β expression peaked at 2 weeks and then gradually declined. In all three groups, the dynamics of MMP-8 concentration were non-linear, increasing by 2 weeks and then declining to below baseline ( > 0.05). and declined within the first month and increased thereafter, not regaining the baseline level. Adjunctive antiseptic treatment was associated with changes in biomarkers and bacterial counts in the course of the study. The effects of adjunctive antiseptic irrigation were limited in the applied protocol.
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http://dx.doi.org/10.3390/dj8040124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712355PMC
November 2020

MMP-8, TRAP-5, and OPG Levels in GCF Diagnostic Potential to Discriminate between Healthy Patients', Mild and Severe Periodontitis Sites.

Biomolecules 2020 10 30;10(11). Epub 2020 Oct 30.

Department of Conservative Dentistry, Faculty of Dentistry, University of Chile, Santiago 8380544, Chile.

Biomarkers represent promising aids in periodontitis, host-mediate diseases of the tooth-supporting tissues. We assessed the diagnostic potential of matrix metalloproteinase-8 (MMP-8), tartrate-resistant acid phosphatase-5 (TRAP-5), and osteoprotegerin (OPG) to discriminate between healthy patients', mild and severe periodontitis sites. Thirty-one otherwise healthy volunteers with and without periodontal disease were enrolled at the Faculty of Dentistry, University of Chile. Periodontal parameters were examined and gingival crevicular fluid was sampled from mild periodontitis sites (M; = 42), severe periodontitis sites (S; = 59), and healthy volunteer sites (H; = 30). TRAP-5 and OPG were determined by commercial multiplex assay and MMP-8 by the immunofluorometric (IFMA) method. STATA software was used. All biomarkers showed a good discrimination performance. MMP-8 had the overall best performance in regression models and Receiver Operating Characteristic (ROC) curves, with high discrimination of healthy from periodontitis sites (area under the curve (AUC) = 0.901). OPG showed a very high diagnostic precision (AUC ≥ 0.95) to identify severe periodontitis sites (S versus H + M), while TRAP-5 identified both healthy and severe sites. As conclusions, MMP-8, TRAP-5, and OPG present a high precision potential in the identification of periodontal disease destruction, with MMP-8 as the most accurate diagnostic biomarker.
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http://dx.doi.org/10.3390/biom10111500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692260PMC
October 2020

High Expression of MMP-9 in Primary Tumors and High Preoperative MPO in Serum Predict Improved Prognosis in Colorectal Cancer with Operable Liver Metastases.

Oncology 2021 7;99(3):144-160. Epub 2020 Oct 7.

Transplantation and Liver Surgery, Abdominal Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Introduction: The liver metastases of colorectal cancer (CRC) can be surgically treated in selected cases, with continuously improving results. Matrix metalloproteinases (MMPs) contribute to cancer invasion by degrading the extracellular matrix, and elevated levels of MMP-2, MMP-8, and MMP-9 have been detected in several malignancies. Myeloperoxidase (MPO) is a mediator of tissue damage that can oxidatively activate latent MMPs. We evaluated the prognostic value of MMP-2, MMP-8, and MMP-9 in tissue samples of primary tumors and liver metastases and the pre- and postoperative serum levels of MMP-8, MMP-9, and MPO in CRC patients undergoing liver resection.

Methods: Tissue and serum samples were obtained from 111 patients who had primary colorectal tumors and their liver metastases surgically treated at the Helsinki University Hospital between 1988 and 2007. Tissue expression of MMP-2, MMP-8, and MMP-9 in primary tumors and liver metastases was evaluated by immunohistochemistry. Pre- and postoperative serum concentrations of MMP-8, MMP-9, and MPO were determined using a time-resolved immunofluorometric assay or commercially available enzyme-linked immunosorbent assay kits. Clinical data were retrieved from patient records and the Central Statistical Office of Finland. Associations with disease-free survival (DFS) and overall survival (OS) were estimated using Cox regression analysis and the Kaplan-Meier method.

Results: High expression of MMP-9 in colorectal tumor tissue was associated with better DFS (p = 0.010), and high preoperative MPO in serum with improved DFS and OS (p < 0.001 and p = 0.014, respectively). The prognostic significance varied according to gender, age, and the synchronicity of liver metastases.

Conclusion: Low preoperative MPO in serum might identify patients at high risk of recurrence and death after resection of colorectal liver metastases. Elevated preoperative MPO and high expression of MMP-9 in colorectal tumor tissue indicate an improved prognosis. The use of these biomarkers should be adjusted according to clinical characteristics.
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http://dx.doi.org/10.1159/000510609DOI Listing
March 2021

Isolation, characterization and regulation of moonlighting proteases from Candida glabrata cell wall.

Microb Pathog 2020 Dec 30;149:104547. Epub 2020 Sep 30.

Faculty of Biological and Environmental Sciences, Molecular and Integrative Biosciences, The Department of Biochemistry and Biotechniques, University of Helsinki, 00014, Helsinki, Finland.

Candida glabrata (C. glabrata) cell wall proteins play a role in virulence and in initial host immune recognition and responses. We isolated and characterized C. glabrata cell wall proteases from a clinical hospital C. glabrata T-1638 blood isolate and estimated the enzymatic activities and their ability to degrade gelatin and processing proMMP-8 and assess the regulation of these proteases with salt treatment, mercaptoethanol and fermented lingonberry juice from Vaccinium vitis idaea L. The cell wall proteases were enzymatically released from the cell wall and beta- 1,3- bonded proteases were fractioned into 10-50 kDa and >50 kDa fractions with anionic DEAE-sepharose ion-exchange chromatography and gel filtration. Proteins were monitored and analyzed with MDPF- zymography, and five gelatinolytic bands were cut out from a parallel silver-stained gel for the LC- MS/MS analysis. The proteases lacked a signal sequence, indicating that they are moonlighting proteases. Human proMMP-8 activation assays were performed with both fractions and verified by western-immunoblot using aMMP-8 specific antibody. Inhibition of proMMP-8 conversion to the lower molecular active enzyme species were demonstrated with fermented lingonberry juice. The results indicate that moonlighting proteases may play a role in the virulence of C. glabrata.
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http://dx.doi.org/10.1016/j.micpath.2020.104547DOI Listing
December 2020

Local and systemic levels of aMMP-8 in gingivitis and stage 3 grade C periodontitis.

J Periodontal Res 2020 Dec 13;55(6):887-894. Epub 2020 Aug 13.

Department of Oral and Maxillofacial Diseases, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.

The Objective: This study aimed to analyze active matrix metalloproteinase (aMMP-8) levels in gingival crevicular fluid (GCF), saliva and serum in the context of new criteria of gingivitis and stage 3 grade C periodontitis.

The Background: Periodontal disease is an inflammatory process that can result in tooth loss and also is considered a modifying factor for systemic health. Matrix metalloproteinase (MMP)-8 is the major collagenase of periodontal tissue breakdown.

Methods: Totally 83 systemically healthy and non-smoker individuals consisting of 23 periodontally healthy, 20 gingivitis and 40 stage 3 periodontitis, were recruited to the study. Clinical periodontal examinations of probing depth (PD), clinical attachment loss (CAL), gingival index (GI), plaque index (PI) and bleeding on probing (BOP) were recorded; and GCF, saliva and serum samples were obtained. aMMP-8 was measured by immunofluorometric assay (IFMA).

Results: GCF and serum aMMP-8 levels were significantly increased in periodontitis and gingivitis compared to healthy ones (P < .001), whereas gingivitis and periodontitis patients showed similar levels of aMMP-8 in GCF and serum (P > .05). Saliva levels of aMMP-8 were higher in periodontitis patients than both gingivitis and healthy individuals (P < .001). There was no significant difference in salivary aMMP-8 levels between gingivitis group and healthy controls (P > .05).

Conclusion: These findings support the involvement of aMMP-8 in periodontal diseases and suggest that its local and systemic levels can reflect stage 3 grade C periodontitis. Moreover, aMMP-8 in GCF and serum seems to have a potential to differentiate between gingivitis and periodontal health.
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http://dx.doi.org/10.1111/jre.12781DOI Listing
December 2020

aMMP-8 Point-of-Care/Chairside Oral Fluid Technology as a Rapid, Non-Invasive Tool for Periodontitis and Peri-Implantitis Screening in a Medical Care Setting.

Diagnostics (Basel) 2020 Aug 5;10(8). Epub 2020 Aug 5.

Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, PO Box 63 (Haartmaninkatu 8), FI-00014 Helsinki, Finland.

This communication article addresses currently available rapid non-invasive methods to screen and detect periodontitis and dental peri-implantitis. In this regard, oral fluid biomarkers have been researched extensively but self-reported oral health (SROH)-questionnaires have also been developed. Both alternatives may offer a quick and easy way to screen and detect diseased patients. Active matrix metalloproteinase (aMMP-8) is one of the most validated biomarkers for screening and detecting periodontal breakdown related to periodontitis and peri-implantitis and monitoring their treatment effects revealing successful, less- and non-successful treatment results. Currently available aMMP-8 lateral-flow technologies allow this kind of analysis, as demonstrated here, to be conducted quantitatively online and real-time as point-of-care/chairside testing in dental and even medical care settings. In this study, an aMMP-8 peri-implant sulcular fluid point-of-care-test diagnosed peri-implantitis and healthy implants far more accurately than bleeding-on-probing or the other biomarkers, such as polymorphonuclear (PMN)/neutrophil elastase, myeloperoxidase and MMP-9. Although, SROH-questionnaires allow screening in similar settings but they lack the information about the current disease activity of periodontitis and peri-implantitis, which is of essential value in periodontal diagnostics and treatment monitoring. Thus, both methods can be considered as adjunct methods for periodontitis and peri-implant diagnostics, but the value of oral fluid biomarkers analysis does not seem to be substitutable.
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http://dx.doi.org/10.3390/diagnostics10080562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460514PMC
August 2020

An Oral Rinse Active Matrix Metalloproteinase-8 Point-of-Care Immunotest May Be Less Accurate in Patients with Crohn's Disease.

Biomolecules 2020 03 4;10(3). Epub 2020 Mar 4.

Department of Periodontology, Institute of Dentistry, University of Turku, 20520 Turku, Finland.

The diagnostic accuracy of point-of-care (PoC) applications may be compromised in individuals with additional inflammatory conditions. This cross-sectional study examined the performance of a commercial oral rinse active matrix metalloproteinase-8 (aMMP-8) PoC immunotest in individuals with ( = 47) and without Crohn's disease (CD) ( = 41). Oral rinse collected from the participants was analyzed by the PoC immunotest. Molecular forms and fragments of salivary MMP-8 were detected by western immunoblotting. The sensitivity of the immunotest for periodontitis was 60.0% in the CD group and 90.0% in the control group. The respective specificity was 75.0% and 80.0%. In both groups, clinical diagnosis of periodontitis exhibited a significant association with the immunotest results, however, the odds ratio (OR) was more than ten-fold in controls (OR 54.3, 95% CI: 3.1-953, = 0.006) in comparison to CD patients (OR 5.2, 95% CI: 1.3-21.6, = 0.022). According to Western immunoblot results, the immunotest MMP-8 positivity was not related to elevated levels of molecular forms and fragments of MMP-8 in the CD group, as in the control group. The diagnostic accuracy of the aMMP-8 PoC oral rinse immunotest is reduced in CD patients, which may be related to lower levels or undetectable complexes.
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http://dx.doi.org/10.3390/biom10030395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175303PMC
March 2020

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

Proteomics Clin Appl 2020 05 7;14(3):e1900050. Epub 2020 Jan 7.

Section of Periodontology and Dental Prevention, Division of Oral Diseases, Department of Dental Medicine, Karolinska Institutet, Alfred Nobels allé 8, 14152, Huddinge, Stockholm, Sweden.

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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http://dx.doi.org/10.1002/prca.201900050DOI Listing
May 2020

The Potential Role of Matrix Metalloproteinases 8 and 9 and Myeloperoxidase in Predicting Outcomes of Bacterial Meningitis of Childhood.

Mediators Inflamm 2019 3;2019:7436932. Epub 2019 Nov 3.

Children's Hospital, Pediatric Research Center, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.

Background: Matrix metalloproteinases (MMPs) and myeloperoxidase (MPO) contribute to the inflammatory cascade in the cerebrospinal fluid (CSF) during bacterial meningitis. We determined levels of MPO, MMP-8, MMP-9, and tissue inhibitor of metalloproteinase- (TIMP-) 1 in the CSF of children with bacterial meningitis and investigated how these inflammatory mediators relate to each other and to the disease outcomes.

Methods: Clinical data and the diagnostic CSF samples from 245 children (median age eight months) with bacterial meningitis were obtained from a clinical trial in Latin America in 1996-2003. MMP-9 levels in the CSF were assessed by zymography, while MMP-8, MPO, and TIMP-1 concentrations were determined with immunofluorometric and enzyme-linked immunosorbent assays.

Results: MPO correlated positively with MMP-8 (rho 0.496, < 0.001) and MMP-9 (rho 0.153, = 0.02) but negatively with TIMP-1 (rho -0.361, < 0.001). MMP-8 emerged as the best predictor of disease outcomes: a CSF MMP-8 concentration above the median increased the odds of death 4.9-fold (95% confidence interval 1.8-12.9).

Conclusions: CSF MMP-8 presented as an attractive prognostic marker in children with bacterial meningitis.
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http://dx.doi.org/10.1155/2019/7436932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6874999PMC
May 2020

Prediabetes/Diabetes Can Be Screened at the Dental Office by a Low-Cost and Fast Chair-Side/Point-of-Care aMMP-8 Immunotest.

Diagnostics (Basel) 2019 Oct 17;9(4). Epub 2019 Oct 17.

Department of Preventive Dentistry, Periodontology and Implant Biology, Dental School, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.

Pre-diabetes and diabetes are strongly associated with periodontal disease (gingivitis and periodontitis), and these conditions are known to upregulate aMMP-8 in inflamed gingiva and oral fluids. Thus, it would be feasible to screen for prediabetes and diabetes at the dental office by chairside tests. Chair-side assessment of HbA and a quantitative point-of-care (PoC) active matrix metalloproteinase (aMMP)-8 oral rinse immunotest developed for periodontal diseases, were performed on patients ( = 69) attending a Periodontology University Clinic who fulfilled the criteria for testing according to the screening questionnaire of the Centers for Disease Control and Prevention, USA. Clinical parameters of periodontal disease were also recorded with an automated probe. Twenty seven-point-five percent of the subjects were found with previously unknown hyperglycemia (HbA1c ≥ 5.7%). There was a statistically-significant positive association between the aMMP-8test and prediabetes ( < 0.05, unadjusted and adjusted for BMI and age ≥ 45 years logistic regression models). The dental setting is suitable for opportunistic screening for undiagnosed diabetes and pre-diabetes and point-of-care HbA1c, especially when combined with aMMP-8 assessment by dental professionals, being convenient and effective.
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http://dx.doi.org/10.3390/diagnostics9040151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6963402PMC
October 2019

On the diagnostic discrimination ability of mouthrinse and salivary aMMP-8 point-of-care testing regarding periodontal health and disease.

Diagn Microbiol Infect Dis 2019 Dec 26;95(4):114871. Epub 2019 Jul 26.

Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, PO Box 63, (Haartmaninkatu 8), FI-00014, Helsinki, Finland; Division of Periodontology, Department of Dental Medicine, Karolinska Institutet, Stockholm SE-171 77, Sweden.

This study investigated the diagnostic utility of mouthrinse and saliva in aMMP-8 measurements to analyze patients' risk for active periodontal tissue destruction and progression of periodontal disease among 47 adolescents. Results show that measurements from mouthrinse produce better discrimination and should be used instead of saliva measurements.
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http://dx.doi.org/10.1016/j.diagmicrobio.2019.114871DOI Listing
December 2019

A point-of-care test of active matrix metalloproteinase-8 predicts triggering receptor expressed on myeloid cells-1 (TREM-1) levels in saliva.

J Periodontol 2020 01 12;91(1):102-109. Epub 2019 Aug 12.

Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: This cross-sectional study aims to investigate if a point-of-care (PoC) test of active matrix metalloproteinase-8 (aMMP-8) predicts levels of inflammation amplifier triggering receptor expressed on myeloid cells-1 (TREM-1) and its putative ligand the neutrophil peptidoglycan recognition protein 1 (PGLYRP1) in saliva.

Methods: Forty-seven adolescents, aged 15 to 17 years, were tested with aMMP-8 PoC test, which was followed by a full-mouth clinical examination of the assessment of periodontal, mucosal, and oral health. TREM-1 and PGLYRP1 levels were analyzed by ELISA. The immunofluorometric assay (IFMA) specific for aMMP-8 was used as the reference method.

Results: Fourteen saliva samples out of a total of 47 showed positivity for aMMP-8 PoC test. Both the TREM-1 and the aMMP-8 (IFMA) levels were significantly elevated among the aMMP-8 PoC test positives compared with the PoC test negatives (P < 0.05). Moreover, aMMP-8 levels assessed by IFMA showed a strong positive correlation with TREM-1 levels in saliva (r = 0.777, P < 0.001). The number of sites with a probing depth of ≥4 mm was significantly lower among the adolescents that had a negative aMMP-8 PoC test result, and TREM-1 levels < 75 pg/mL (P < 0.05). In contrast, adolescents with a positive aMMP-8 PoC test result (i.e., elevated aMMP-8 levels) together with elevated TREM-1 levels had a significantly higher number of periodontal pockets with ≥4 mm (P < 0.001).

Conclusion: The present study validated usability of aMMP-8 PoC test for predicting "proinflammatory" salivary profile and periodontal health status in adolescents.
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http://dx.doi.org/10.1002/JPER.19-0132DOI Listing
January 2020

High levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) in the serum are associated with poor prognosis in HPV-negative squamous cell oropharyngeal cancer.

Cancer Immunol Immunother 2019 Aug 25;68(8):1263-1272. Epub 2019 Jun 25.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Helsinki and HUS Helsinki University Hospital, P.O.Box 263, 00029 HUS, Helsinki, Finland.

Background: An emerging subset of oropharyngeal squamous cell carcinomas (OPSCC) is caused by HPV. HPV-positive OPSCC has a better prognosis than HPV-negative OPSCC, but other prognostic markers for these two different diseases are scarce. Our aim was to evaluate serum levels and tumor expression of matrix metalloproteinase-8 (MMP-8) and tissue inhibitor of metalloproteinase-1 (TIMP-1) and to assess their prognostic role in HPV-positive and HPV-negative OPSCC.

Materials And Methods: A total of 90 consecutive OPSCC patients diagnosed and treated with curative intent at the Helsinki University Hospital between 2012 and 2016 were included. Serum samples were prospectively collected. An immunofluorometric assay and an enzyme-linked immunosorbent assay were used to determine MMP-8 and TIMP-1 serum concentrations, respectively. HPV status of the tumors was determined using a combination of HPV-DNA genotyping and p16-INK4a immunohistochemistry. The endpoints were overall survival (OS) and disease-free survival (DFS).

Results: High TIMP-1 serum levels were strongly and independently associated with poorer OS (adjusted HR 14.7, 95% CI 1.8-117.4, p = 0.011) and DFS (adjusted HR 8.7, 95% CI 1.3-57.1, p = 0.024) among HPV-negative patients; this association was not observed in HPV-positive OPSCC. Although TIMP-1 was immunoexpressed in the majority of the tumor tissue samples, the level of immunoexpression was not associated with prognosis, nor did MMP-8 serum levels.

Conclusion: Our results indicate that serum TIMP-1 levels may serve as an independent prognostic marker for HPV-negative OPSCC patients.
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http://dx.doi.org/10.1007/s00262-019-02362-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682571PMC
August 2019

Active Matrix Metalloproteinase-8 Point-of-Care (PoC)/Chairside Mouthrinse Test vs. Bleeding on Probing in Diagnosing Subclinical Periodontitis in Adolescents.

Diagnostics (Basel) 2019 Mar 23;9(1). Epub 2019 Mar 23.

Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, P.O. Box 63 (Haartmaninkatu 8), 00014 Helsinki, Finland.

This cross-sectional study compares the effectiveness of an active MMP-8 (aMMP-8) point-of-care (PoC)/chairside mouthrinse test to the conventional bleeding on probing (BOP) (cutoff 20%) test in detecting subclinical periodontitis/pre-periodontitis in Finnish adolescents. The study was carried out at the Kotka Health Center, Finland. A total of 47 adolescents (30 boys/17 girls) aged 15⁻17 were first tested with the aMMP-8 PoC test, followed by a full-mouth evaluation of clinical parameters of oral health including periodontal, oral mucosal, and caries assessment. A periodontist performed these clinical examinations. The aMMP-8 PoC test result had much stronger association with subclinical periodontitis than the BOP 20% test (2.8⁻5.3 times stronger in terms of odds ratio). The aMMP-8 PoC test had ≥2 times higher sensitivity than the BOP 20% test with, generally, the same specificity. Further, the aMMP-8 PoC test had generally better accuracy and lower false negative percentages. The aMMP-8 PoC test seemed to be more effective than the conventional BOP test in detecting subclinical periodontitis/pre-periodontitis in adolescents reducing the risk of their undertreatment. However, the sample size may be a limiting factor, and more studies are needed to confirm our results for both adolescents and adults.
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http://dx.doi.org/10.3390/diagnostics9010034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468891PMC
March 2019

Adjunctive Effects of a Sub-Antimicrobial Dose of Doxycycline on Clinical Parameters and Potential Biomarkers of Periodontal Tissue Catabolism.

Dent J (Basel) 2019 Jan 20;7(1). Epub 2019 Jan 20.

Department of Oral and Maxillofacial Diseases, University of Helsinki, Helsinki University Hospital, Helsinki 00014, Finland.

Objectives: The aim of the present randomized, double-blind, placebo-controlled, parallel-arm study was to examine the effectiveness of a sub-antimicrobial dose of doxycycline (SDD) in combination with nonsurgical periodontal therapy, compared to nonsurgical periodontal therapy alone, on potential gingival crevicular fluid (GCF) biomarkers of periodontal tissue catabolism related to the clinical outcomes over a 12-month period. GCF was collected and clinical parameters were recorded from 30 periodontitis patients randomized either to an SDD or placebo group. The SDD group received SDD (20 mg) b.i.d for 3 months plus scaling and root planing (SRP), while the placebo group was given placebo capsules b.i.d for 3 months plus SRP. The patients were evaluated every 3 months during the 12-month study period. At each visit, clinical parameters and GCF sampling were repeated. Matrix metalloproteinase (MMP)-8, MMP-9, MMP-13, myeloperoxidase (MPO), osteoprotegerin (OPG), and tartrate-resistant acid phosphatase-5 (TRAP-5) were determined by IFMA and ELISA. Significant improvements were observed in all clinical parameters in both groups over 12 months ( < 0.0125) while the SDD group showed significantly better reduction in gingival index (GI) and pocket depth and a gain in clinical attachment compared to the placebo group ( < 0.05). GCF MMP-8 and OPG levels significantly reduced in the SDD group compared to baseline ( < 0.05). GCF MMP-9 significantly decreased in both groups compared to baseline ( < 0.05). GCF MPO significantly decreased at 3 and 9 months in the SDD group, while it significantly decreased at 6 months in the placebo group ( < 0.05). TRAP and MMP-13 could be detected in none of the samples. The present results indicate that three months of adjunctive usage of SDD to nonsurgical periodontal therapy compared to nonsurgical periodontal therapy alone in periodontitis patients results in further improvement of clinical periodontal parameters and GCF markers of periodontal tissue breakdown over a 12-month period. Beneficial effects of adjunctive SDD therapy is likely to be related to the reduced levels of two major periodontitis-associated MMPs, MMP-8 and -9, and their potential oxidative activator MPO.
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http://dx.doi.org/10.3390/dj7010009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6473443PMC
January 2019

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

Cytokine 2019 03 6;115:135-141. Epub 2019 Jan 6.

Section of Periodontology, Department of Dentistry and Oral Health, Aarhus University, Aarhus, Denmark.

Aim: This study aimed to investigate the association between salivary levels of myeloperoxidase (MPO), neutrophil elastase (NE), soluble urokinase-type plasminogen activator receptor (suPAR), matrix metalloproteinase (MMP)-8 and tissue inhibitor of matrix metalloproteinases (TIMP)-1 and gingival inflammation development during an experimental gingivitis study.

Methods: A three-week experimental gingivitis study was conducted. Clinical recordings of dental plaque biofilm (Modified Quigley Hein Plaque Index, TQHPI) and gingival inflammation (Modified Gingival Index, MGI) were made at specific time points for each of the 42 participants. Salivary levels of MPO, NE, suPAR, MMP-8 and TIMP-1 at the same time points were measured using distinct immunoassays. For data analysis growth curve modelling was employed to account for the time-varying outcome (MGI score) and the time-varying covariates (salivary marker levels, and TQHPI score). Analyses were stratified according to the MGI-score trajectory groups previously identified as 'fast', respectively 'slow' responders.

Results: Overall, higher MGI scores were statistically significantly positively associated with higher levels of MPO, MMP-8 and TIMP-1. Stratified analysis according to inflammation development trajectory group revealed higher levels of salivary MPO, MMP-8 and MMP-8/TIMP-1 ratio among the 'fast' responders than among 'slow' responders. None of the investigated salivary protein markers was associated with a 'slow' inflammation development response.

Conclusions: Salivary levels of MPO, MMP-8 and TIMP-1 were associated with the extent and severity of gingival inflammation. While the 'fast' gingival inflammation response was associated with increased levels of MPO, MMP-8 and MMP-8/TIMP-1 ratio, the 'slow' response was not associated with any of the salivary protein markers investigated in this study. Neutrophil activity seems to orchestrate a 'fast' gingival inflammatory response among participants previously primed to gingival inflammation.
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http://dx.doi.org/10.1016/j.cyto.2018.12.002DOI Listing
March 2019

Enhanced Systemic Response of Matrix Metalloproteinases and Their Regulators in and Patients.

Diagnostics (Basel) 2018 Dec 13;8(4). Epub 2018 Dec 13.

Department of Medical Sciences, Clinical Microbiology, Uppsala University, Dag Hammarskjölds väg 38, 75237 Uppsala, Sweden.

Campylobacters are major enteropathogens worldwide with a substantial financial burden. Matrix metalloproteinases (MMPs) are proteolytic metalloendopeptidases with ability to modify immune response and shown to be upregulated in patients with several tissue destructive diseases, including infections. We measured here serum concentrations of MMP-8 and MMP-9 together with their regulators myeloperoxidase (MPO), human neutrophil elastase (HNE), and tissue inhibitor of metalloproteinases (TIMP)-1 in 80 and 25 patients as well as in 27 healthy controls. Paired serum samples were available for 73 and 23 patients, respectively. When the initial serum samples were compared to those from controls, both and patients showed elevated concentrations of all biomarkers tested ( ≤ 0.037). In the follow-up samples, collected about 25 days afterwards, MMP-8 levels of patients had already turned to normal but all the other biomarkers still showed elevated, although from the initial levels significantly dropped, levels. For the follow-up samples of patients, only MMP-9 and MPO levels were at a significantly higher level than in controls. It remains to be studied if the systematically enhanced neutrophil-derived proteolytic and oxidative stress, induced by infection as shown here and persisting for several weeks, is important for the development of late sequelae.
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http://dx.doi.org/10.3390/diagnostics8040082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315616PMC
December 2018

Serum matrix metalloproteinase 8 and tissue inhibitor of metalloproteinase 1: Potential markers for malignant transformation of recurrent respiratory papillomatosis and for prognosis of laryngeal cancer.

Head Neck 2019 02 14;41(2):309-314. Epub 2018 Dec 14.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: Biomarkers that could predict malignant transformation of recurrent respiratory papillomatosis (RRP) would be useful in patient follow-up. We investigated whether serum matrix metalloproteinase 8 (MMP-8) and tissue inhibitor of metalloproteinase 1 (TIMP-1) could predict malignant transformation of RRP and whether they associate with survival in laryngeal squamous cell carcinoma (LSCC) without preexisting RRP.

Methods: We analyzed serum MMP-8 (S-MMP-8) and serum TIMP-1 (s-TIMP-1) in 114 patients: 55 were treated for RRP and 59 for LSCC without preexisting RRP. Five patients with RRP developed LSCC during follow-up.

Results: Elevated S-MMP-8 level in RRP was associated with malignant transformation (P = .01). Compared to patients with RRP, S-MMP-8 in patients with LSCC was significantly higher (P < .001). Increased S-TIMP-1 level in LSCC was associated with poor overall survival (P = .02) and recurrence-free survival (P = .05).

Conclusion: In RRP, high S-MMP-8 may predict malignant transformation. In LSCC, elevated S-TIMP-1 is connected to poor survival.
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http://dx.doi.org/10.1002/hed.25459DOI Listing
February 2019

High serum MMP-14 predicts worse survival in gastric cancer.

PLoS One 2018 7;13(12):e0208800. Epub 2018 Dec 7.

Research Programs Unit, Translational Cancer Biology, University of Helsinki, Helsinki, Finland.

Matrix metalloproteinases (MMPs), endopeptidases with diverse biochemical functions, can promote cancer cell invasion and metastasis by degrading the extracellular matrix. A high matrix metalloproteinase-14 (MMP-14) expression in gastric cancer tissue has been associated with metastasis and poor prognosis. To further understand this association, we investigated serum MMP-14 as a biomarker in gastric cancer patients. The patient cohort consisted of 240 gastric adenocarcinoma patients who underwent surgery at Helsinki University Hospital, Finland, between 2000 and 2009. We determined the soluble MMP-14 serum levels using an enzyme-linked immunosorbent assay. We then calculated the associations between serum levels and clinicopathologic variables using the Mann-Whitney U-test or the Kruskal-Wallis test. We constructed survival curves using the Kaplan-Meier method and calculating the hazard ratios using the Cox proportional hazard model. We revealed a positive association between a high serum MMP-14 level and stages III-IV (p = 0.029), and between a high serum MMP-14 and distant metastasis (p = 0.022). Patients with a low serum MMP-14 had a 5-year disease-specific survival of 49.2% (95% confidence interval [CI] 45.5-52.9), whereas patients with a high serum MMP-14 had a 5-year survival of 22.1% (95% CI 15.2-29.0; p = 0.001). High serum MMP-14 was a statistically significant prognostic factor among patients with an intestinal type of cancer (hazard ratio [HR] 3.54; 95% CI 1.51-8.33; p = 0.004), but not among patients with a diffuse type. The serum MMP-14 level remained an independent prognostic factor in our multivariate survival analysis (HR 1.55; 95% CI 1.02-2.35; p = 0.040). This study indicates for the first time that high serum soluble MMP-14 levels in gastric cancer serves as a marker for a poor prognosis, possibly indicating the presence of distant metastases.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0208800PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6285995PMC
May 2019

Smoking confounds the periodontal diagnostics using saliva biomarkers.

J Periodontol 2019 05 14;90(5):475-483. Epub 2018 Dec 14.

Department of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Finland.

Background: Smoking is a risk factor for periodontal disease because of its complex impact on the inflammatory response in the periodontium. We investigated the effect of smoking on salivary periodontal biomarkers, matrix metalloproteinase (MMP)-8, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 and myeloperoxidase (MPO).

Methods: Saliva biomarkers were analyzed in the Parogene population (n = 480) comprising a random cohort of patients that have undergone coronary angiography and oral examination. The effect of time since cessation and pack years of smoking on biomarkers were investigated.

Results: Saliva MMP-8, MMP-9, TIMP-1, and MPO concentrations distinguished periodontitis patients significantly from patients without periodontitis. When the time since cessation was considered, the area-under-the-curve values (p-value) for periodontitis were 0.76 (<0.001), 0.74 (<0.001), 0.70 (<0.001), and 0.76 (<0.001), respectively. Adding information about smoking habits in the models improved slightly the sensitivities of all biomarkers. In logistic regression model saliva, MMP-8 was mainly affected by pack years of smoking, whereas saliva MMP-9, TIMP-1, and MPO were mostly affected by time since cessation, especially if smoking currently or quit recently (<1 year ago).

Conclusion: Smoking confounds the salivary diagnostics of periodontitis and should be considered when interpreting the results obtained by potential diagnostic tests.
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http://dx.doi.org/10.1002/JPER.18-0545DOI Listing
May 2019

Cross-sectional analysis of risk factors for subclinical periodontitis; active matrix metalloproteinase-8 as a potential indicator in initial periodontitis in adolescents.

J Periodontol 2019 05 28;90(5):484-492. Epub 2018 Nov 28.

Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: The aim of this study was to investigate how different patient-related risk indicators might be associated with the odds of developing subclinical periodontitis in adolescents.

Methods: This cross-sectional study included 252 Finnish individuals aged 15 to 16 years, of whom 141 were boys and 111 girls. A specially trained dentist performed clinical examinations: measurements included periodontal indexes (bleeding on probing, visible plaque index, root calculus, and probing depth, smoking by pack-years, periodontal bacteria (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Prevotella intermedia, Prevotella nigrescens, and Treponema denticola) and the potential salivary periodontal biomarkers (active matrix metalloproteinase-8 [aMMP-8], polymorphonuclear leukocyte elastase [PMN elastase], and total protein, albumin, immunoglobulin A, immunoglobulin G, and immunoglobulin M). Results were analyzed by ordinal logistic regression, one-way analysis of variance, Fisher exact test, and Kruskal-Wallis H test.

Results: The main finding of this study was that subclinical periodontitis in adolescents was statistically significantly associated with elevated salivary aMMP-8 but not with PMN elastase. Also, adolescents with subclinical periodontitis had statistically significantly higher levels of bleeding on probing, root calculus, and dental plaque than adolescents without subclinical periodontitis.

Conclusions: We suggest that the main risk factor for subclinical periodontitis in adolescents is the partly calcified, dysbiotic bacterial biofilm, which interacts with the immune defenses of the host; this leads to gingival inflammation and eventually to deepening periodontal pockets. This proinflammatory subclinical periodontitis stage, which represents stage I periodontitis in the new classification, is reflected as elevated salivary aMMP-8 levels in oral fluids.
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http://dx.doi.org/10.1002/JPER.18-0450DOI Listing
May 2019

Point-of-Care/Chairside aMMP-8 Analytics of Periodontal Diseases' Activity and Episodic Progression.

Diagnostics (Basel) 2018 Oct 22;8(4). Epub 2018 Oct 22.

Division of Periodontology, Department of Dental Medicine, Karolinska Institute, SE-171 77 Stockholm, Sweden.

Traditional periodontal disease diagnostics are based mainly on clinical examination and radiographs. They assess only past tissue destruction and provide no information on the current disease status or its future progression. The objective is to find out if an active matrix metalloproteinase-8 (aMMP-8) point-of-care (PoC) test could provide a cost-effective way to get around this limitation. This cross-sectional study used 47 adolescents and 70 adults, who were clinically examined and their aMMP-8 PoC tested. The aMMP-8 PoC test results and patients' treatment need, based on the community periodontal index of treatment needs (CPITN), were compared and analyzed using Fisher's exact test. In terms of CPITN, the aMMP-8 PoC test gave no false positives for both adolescents and adults. All healthy patients got a negative test result, while a positive test result indicated periodontal treatment need correctly. Finally, there was a significant association between a patient's aMMP-8 PoC test result and his/her treatment need ( = 0.001 for adolescents, = 0.001 for adults). In conclusion, more accurate diagnostics of periodontal diseases' activity and progression using an aMMP-8 PoC test may help to reduce oral health care costs by reducing patient overtreatment, improving patient outcome, and reducing the need for complex periodontal therapy.
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http://dx.doi.org/10.3390/diagnostics8040074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315514PMC
October 2018

Molecular forms and fragments of salivary MMP-8 in relation to periodontitis.

J Clin Periodontol 2018 12 18;45(12):1421-1428. Epub 2018 Nov 18.

Department of Oral and Maxillofacial Disease, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.

Aim: To investigate the molecular forms of salivary matrix metalloproteinase (MMP)-8 in relation to periodontitis.

Materials And Methods: Molecular forms, degree of activation and fragmentation of neutrophilic and mesenchymal-type MMP-8 isoforms were analysed from salivary samples of 81 subjects with generalized periodontitis, 63 subjects with localized periodontitis and 79 subjects without pocket teeth, by using western-immunoblots with computer quantitation. In addition, human recombinant proMMP-8 was in vitro activated by Treponema denticola chymotrypsin-like protease (Td-CTLP), sodium hypochlorite (NaOCl, 1 mM, oxidant) or amino phenyl mercuric acetate (APMA, 1 mM).

Results: In saliva of periodontitis-affected individuals, MMP-8 is found in multiple forms, that is, complexes, active and pro-forms of neutrophilic and mesenchymal-type MMP-8, and especially 20-27 kDa fragments. The quantity of these fragments was elevated in both localized and generalized forms of periodontitis. Moreover, the tested activators (Td-CTLP, NaOCl and APMA) activated inactive proMMP-8, resulting in fragments of 20-27 kDa, in vitro, and salivary concentrations of T. denticola correlated significantly with salivary levels of fragmented MMP-8.

Conclusion: The present results indicate that during the development and progression of periodontitis, MMP-8 appears as activated and fragmented, and treponemal proteases most likely play role in this cascade.
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http://dx.doi.org/10.1111/jcpe.13024DOI Listing
December 2018