Salivary MMP-8 Levels Research Articles

Investigating the role of salivary Interleukin-40 levels in diagnosing periodontal diseases.

The present study aimed to analyze IL-40, IL-1β, and MMP-8 levels in periodontitis as well as gingivitis and periodontal health, and to explore potential correlations between these biomarkers and standard clinical parameters. We collected saliva samples from 120 systemically healthy, non-smoking individuals aged between 18 and 63 years. These individuals were divided into three groups: healthy controls [S], gingivitis [G], and stage III grade B periodontitis [P]. IL-40, IL-1β, and MMP-8 levels in saliva samples were analyzed by ELISA. We observed significantly elevated salivary IL-40 levels in the G group compared to the S group (p = 0.003). We found significantly higher salivary IL-1β levels in the P group compared to both the S and G groups (p = 0.000). Salivary MMP-8 levels were significantly higher in the P group than in the S group (p = 0.016). Our study suggests that IL-40 and IL-1β may serve as effective salivary biomarkers for diagnosing gingivitis, while MMP-8 and IL-1β may be effective for distinguishing periodontitis. Based on our study's findings, it can be stated that IL-40 may serve as a new and effective biomarker for distinguishing individuals with gingivitis from healthy ones.

Relationship between the salivary concentration of matrix metalloproteinases 8 and 20 and severe early childhood caries.

Dental caries is initiated through mineral dissolution by bacterial acids and collagen degradation by endogenous proteolytic enzymes, mainly collagenolytic matrix metalloproteinases (MMPs). The present research aimed to evaluate the relationship between severe early childhood caries (S-ECC) and salivary MMP-8 and MMP-20 concentrations. Fifty children aged 36-60 months were assigned to either the caries-free (control) group or the S-ECC group. Standard clinical examinations were performed, and approx. 1 mL of expectorated unstimulated whole saliva was collected from all participants. In the S-ECC group, the sampling was repeated 3 months after restorative treatment. All samples were analyzed for the salivary concentrations of MMP-8 and MMP-20, using the enzyme-linked immunosorbent assay (ELISA). Statistical analysis employed the t test, the Mann-Whitney U test, the χ2 test, Fisher's exact test, and the paired samples t test. The level of significance was set at 0.05. At baseline, the subjects in the S-ECC group presented with significantly elevated levels of MMP-8 as compared to the control group. However, the salivary concentration of MMP-20 did not exhibit a significant difference between the 2 groups. A significant reduction occurred in the levels of MMP-8 and MMP-20 3 months after restorative treatment in the S-ECC group. The salivary levels of MMP-8 and MMP-20 were significantly affected by dental restorative treatment in children. Furthermore, MMP-8 was observed to be a better indicator of the dental caries status than MMP-20.

Peri-Implant Surgical Treatment Downregulates the Expression of sTREM-1 and MMP-8 in Patients with Peri-Implantitis: A Prospective Study.

sTREM-1 and its ligand PGLYRP1 play an essential role in the inflammatory process around teeth and implants. In this study, we aimed to evaluate the impact of peri-implant treatment on the salivary levels of the sTREM-1/PGLYRP-1/MMP-8 axis after 3 months. A total of 42 participants (with a mean age of 61 years old ± 7.3) were enrolled in this longitudinal study, 24 having peri-implant mucositis (MU) and 18 having peri-implantitis (PI). Clinical peri-implant parameters, such as probing pocket depth (PPD), % of plaque, and bleeding on probing (BOP), and the whole unstimulated saliva samples were evaluated at baseline and 3 months after treatment. The MU group received nonsurgical peri-implant treatment, while the PI group received open-flap procedures. The levels of sTREM-1, PGLYRP-1, MMP-8, and TIMP-1 were analyzed using enzyme-linked immunosorbent assays. BOP, plaque levels, and PPD significantly reduced after treatment in both groups. A significant decrease in the salivary levels of sTREM-1, MMP-8, and TIMP-1 in the PI group and PGLYRP1 and TIMP-1 in the MU group were observed. Salivary levels of sTREM-1 were significantly reduced in patients with PI but not with MU. Additionally, peri-implant treatment had a significantly higher impact on MMP-8 reduction in patients with PI than in those with MU.

Linking oral microbial proteolysis to aMMP-8 PoC diagnostics along with the stage and grade of periodontitis: A cross-sectional study.

Linking oral microbial proteolysis to aMMP-8 PoC diagnostics along with the stage and grade of periodontitis: A cross-sectional study.

Impact of Non-surgical Periodontal Therapy on Pulmonary functions, Periodontal Health and Salivary Matrix Metalloproteinase-8 of COPD Patients with Chronic Periodontitis: A Clinico-biochemical Study.

The aim of the study was to assess the impact of non-surgical periodontal therapy (NSPT) on periodontal clinical parameters, spirometric indices, and salivary MMP-8 levels in patients with chronic obstructive pulmonary disease (COPD) with concurrence of chronic periodontitis (CP) compared with systemically healthy CP. In this prospective clinico-biochemical study, a total of 75 patients belonging to various socioeconomic strata were randomly divided into cases, that is, COPD patients as per the Global Initiative for Obstructive Lung Disease (GOLD) criteria with concurrence of CP [at least ≥ 20 teeth with ≥ 2 tooth sites having pocket probing depth (PPD) or clinical attachment loss (CAL) ≥ 4mm and bleeding on probing (BOP)] and controls (systemically healthy CP). Both groups underwent NSPT and were evaluated for plaque index (PI), gingival index (GI), PPD, CAL, and BOP and spirometry (FEV1/forced vital capacity (FVC)) values at baseline, 3, 6, and 12 months and for salivary MMP-8 levels at baseline and 3 months. Statistical results showed that cases (COPD with CP; n = 37) were significantly older (mean age 56.16 ± 9.01 years), ex-smokers (48.6%) with male preponderance (78.4%), and belonged to the upper middle class (40.5%) as compared to controls (systemically healthy CP; n = 38). After NSPT, significant improvement in mean PI, GI, PPD, CAL, and BOP was observed in both groups at 3, 6, and 12 months with better results in controls. FEV1/FVC was significantly improved (P < .001) in cases with insignificant change in controls at 12 months. After 3 months, MMP-8 levels were significantly reduced in cases (P = .002) and controls (P < .001). The present study provided substantial evidence that COPD patients have poorer periodontal health as compared to systemically healthy counterparts. Further, these patients showed improvement in FEV1/FVC, however, with higher salivary MMP-8 levels despite NSPT at the end of the study, indicating a possible role of systemic inflammatory overburden of pulmonary disease.

An aMMP-8 Point-of-Care and Questionnaire Based Real-Time Diagnostic Toolkit for Medical Practitioners.

The aim of this cross-sectional study is to propose an efficient strategy based on biomarkers adjunct with an interview/questionnaire covering risk factors for periodontitis for the identification of undiagnosed periodontitis by medical professionals. Active matrix metalloproteinase (aMMP)-8 levels in mouthrinse were analyzed by a point-of-care (PoC)/chairside lateral-flow immunotest, and salivary total MMP-8, total MMP-9 and calprotectin levels were analyzed by enzyme-linked immunosorbent assays (ELISAs) and active MMP-9 by gelatin zymography for 149 Greek patients. Patients underwent a full-mouth oral health examination for diagnosis according to the 2018 classification system of periodontal diseases. In addition, patient characteristics (risk factors: age, gender, education level, smoking and body mass index) were recorded. Receiver operating curve (ROC) analysis indicated better diagnostic precision to identify undiagnosed periodontitis for oral fluid biomarkers in adjunct with an interview/questionnaire compared with a plain questionnaire (i.e., risk factors): aMMP-8 AUC (95% confidence interval) = 0.834 (0.761−0.906), total MMP-8 = 0.800 (0.722–0.878), active MMP-9 = 0.787 (0.704–0.870), total MMP-9 = 0.773 (0.687−0.858) and calprotectin = 0.773 (0.687–0.858) vs. questionnaire = 0.764 (0.676–0.851). The findings of this study suggest that oral fluid biomarker analysis, such as a rapid aMMP-8 PoC immunotest, could be used as an adjunct to an interview/questionnaire to improve the precision of timely identification of asymptomatic, undiagnosed periodontitis patients by medical professionals. This strategy appears to be viable for referring patients to a dentist for diagnosis and treatment need assessment.

Salivary Metalloproteinase-8 and Metalloproteinase-9 Evaluation in Patients Undergoing Fixed Orthodontic Treatment before and after Periodontal Therapy.

(1) Background: Metalloproteinase-8 (MMP-8) and metalloproteinase-9 (MMP-9) are members of a family of proteases of major importance during orthodontic tooth movement. Their levels increase during orthodontic therapy and in periodontally affected tissues. Orthodontic fixed appliances retain dental plaque and can cause gingival inflammation. When gingival inflammation is present, the forces produced during orthodontic tooth movement can aggravate tissue reaction and cause the destruction of supportive periodontal tissue. This study aimed to identify biomarkers that facilitate the assessment of periodontal status during orthodontic treatment. (2) Methods: Our study was conducted on 111 patients who were about to receive fixed orthodontic treatment. We determined the salivary levels of MMP-8 and MMP-9 and bleeding on probing (BOP) before applying the orthodontic fixed appliance (T1), one week after appliance placement (T2), and during orthodontic treatment, one month after non-surgical periodontal treatment (T3). (3) Results: Patients undergoing orthodontic treatment show a significant increase in BOP, MMP-8, and MMP-9 levels one week after orthodontic appliance placement (T2) and a decrease in these parameters one month after periodontal treatment (T3). Statistically significant correlations were found between MMP-8 levels and BOP values at T1, T2, and T3. (4) Conclusion: In our study patients undergoing orthodontic treatment show a significant increase in BOP, MMP-8, and MMP-9 levels one week after orthodontic appliance placement and a decrease in these parameters one month after periodontal treatment. Strong positive statistically significant correlations were found between MMP-8 levels and BOP and medium positive statistically significant correlations between MMP-9 and BOP values before and after orthodontic treatment and periodontal treatment. MMP-8, MMP-9, and BOP could be used to assess the periodontal status of orthodontic patients.

Association between isotretinoin (Roaccutanne) use and changes in periodontal clinical parameters and MMP-8 and MMP-9 salivary levels.

Aims: to evaluate changes in clinical periodontal parameters, salivary levels of MMP-8 and MMP-9, in individuals taking Isotretinoin (INN), and compare with individuals not taking the medication and to compare findings among different stages of periodontal disease and healthy periodontium. Material and methods: A case-control study was conducted with a total of 180 human adults divided into six groups. Clinical parameters, including pocket depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP) were measured at six sites per tooth. Whole unstimulated saliva samples were collected from all subjects to detect salivary level of MMP-8, MMP-9 using Enzyme-linked immunosorbent assay (ELISA). Data were analyzed using IBM SPSS Software. Kruskal Wallis test and Mann-Whitney U-tests were used to test any significant differences in any of the groups on all parameters. Pearson Chi-square test was used to compare the distribution of categorical responses across the study groups. All tests were compared at a significance level of 0.05. Results: In Gingivitis cases, INN group was found to have significantly less BOP (P < 0.0001). In Periodontitis cases, INN group showed significant difference in BOP (P < 0.0001). MMP-8 and MMP-9 were significantly lower among Periodontitis cases taking INN compared to the same group not taking the medication (P < 0.0001). Conclusion: INN assists in reducing clinical and biological signs of inflammation related to periodontal disease progression. INN may be a future additive medication to be further evaluated for treating periodontal disease.

Changes in Inflammatory Cytokines in Saliva after Non-Surgical Periodontal Therapy: A Systematic Review and Meta-Analysis.

To determine the diagnostic value of inflammatory cytokines in periodontal disease, we performed a systematic review of the changes in inflammatory cytokines after non-surgical periodontal therapy and a meta-analysis of the utility of interleukin (IL)-1β and matrix metalloproteinase (MMP)-8 as salivary biomarkers. All available papers published in English until 20 August 2020, were searched in the MEDLINE and EMBASE databases. Population, intervention, comparison, and outcome data were extracted from the selected studies, and the roles of IL-1β and MMP-8 were assessed in a meta-analysis. Eleven studies, including two meta-analyses, were assessed in the systematic review. Biomarkers showing high levels in periodontal disease were salivary IL-1β, IL-4, IL-6, MMP-8, and tissue inhibitor of matrix metalloproteinases (TIMP)-2, and those in the controls were tumor necrosis factor (TNF)-α, IL-10, IL-17, and IL-32. Biomarkers that decreased after scaling and root planning (SRP) and oral hygiene instruction (OHI) in periodontitis patients were IL-1β, MMP-8, MMP-9, prostaglandin E2 (PGE2), and TIMP-2. The pooled standardized mean difference of IL-1β and MMP-8 was −1.04 and 35.90, respectively, but the differences between periodontitis patients and healthy controls were not significant. Although the changes in salivary IL-1β and MMP-8 levels after non-surgical periodontal therapy were not significant, salivary cytokines could be used to confirm the effect of periodontal therapy or diagnose periodontal disease.

Importance of MMP-8 in Salivary and Gingival Crevicular Fluids of Periodontitis Patients.

Matrix metalloproteinases (MMPs) stimulate alveolar bone loss in chronic periodontitis. To evaluate the salivary and gingival crevicular fluid (GCF) levels of MMP-8 in patients with moderate to severe chronic periodontitis. 42 participants were divided into two groups: a case group (21 patients with generalized moderate to severe chronic periodontitis) and a control group (21 healthy periodontal subjects). GCF and saliva samples were obtained from both groups. Salivary and GCF MMP-8 levels of each subject were detected using the ELISA method. Mean±SD values of salivary MMP-8 levels of the control and case groups were 1.52 ± 0.65 ng/ml and 6.06 ± 1.18 ng/ml, respectively, and statistically significant difference was observed (p=0.0001). Also, mean±SD values of GCF MMP-8 levels of the control and case groups were 0.87 ± 0.26 ng/ml and 2.92 ± 0.64 ng/ml, respectively; which was statistically significant (p=0.0001). Our results demonstrate an increased concentration of salivary and GCF levels of MMP-8 in the patient group.

Evaluation of Salivary Matrix Metalloproteinase (MMP-8) in Periodontal Patients Undergoing Non-Surgical Periodontal Therapy and Mouthwash Based on Ozonated Olive Oil: A Randomized Clinical Trial.

Background: Extracellular matrix metalloproteinases (MMPs) play a pivotal role in the damage to the periodontal tissue in patients with periodontitis. Scaling and root planning (SRP) attempt to control the plaque amount and consequentially reduce the bacterial load. Non-surgical periodontal treatment could be integrated with drug therapy and physiotherapy procedures such as ozone therapy. The aim of this study was to evaluate in a cohort of patients with a diagnosis of periodontitis: (1) the efficacy of non-surgical periodontal therapy assisted by the use of ozonated olive oil-based mouthwash on salivary metalloproteinase (MMP-8) and (2) the reduction of periodontal indices. Methods: Ninety-six subjects with a diagnosis of periodontitis were enrolled in this study and randomly assigned to the study group (SRP + mouthwash) or control group (SRP). The study duration was 3 months. Data on MMP-8, plaque index (PI), bleeding on probing (BoP) and probing pocket depth (PPD) were recorded at T0, T1 (14 days), T2 (1 month) and T3 (6 months). Group differences were assessed using Student’s t-test for independent samples. Results: A significant improvement in PI, BoP, PPD and salivary MMP-8 levels was observed in both groups. An analysis of differences in relative changes of indices revealed the efficacy of ozonated olive oil in decreasing MMP-8 level. Simultaneously, it slowed the decrease of BoP index. Conclusions: Scaling and root plaining with the aid of ozonated olive oil mouthwash were found to be more effective on salivary MMP-8 reduction than scaling and root plaining alone.

Dentin degradonomics - The potential role of salivary MMP-8 in dentin caries.

BackgroundDentin caries involves dissolution of minerals which eventually leads to degradation of organic matrix. This degradation which was thought to be by bacterial proteases is now considered to be orchestrated by endogenous collagenases such as Matrix Metalloproteinases (MMPs). This paper aims to estimate the salivary levels of MMP-8 in dental caries and also to asses the various risk factors that contribute to the formation of dental caries. Material and MethodsA random sample of 75 adults aged 18-35 were included and categorized based on the number of caries lesions (MCL). Standard clinical examinations were performed, and stimulated saliva was collected and analyzed for concentrations of MMP-8 using enzyme-linked immunosorbent assay. Caries risk factors were assessed using a chair-side kit. Correlation of MMP-8 in varying MCL using Spearman’s correlation was done. Multiple linear regression analysis was done to asses the relationship between various caries risk factors with MMP-8 and MCL as dependent variable. ResultsThe study results showed a statistically significant higher concentration of MMP-8 in carious group (MCL 1-2) and MCL ≥3 compared to non-carious group. On correlating, the levels of MMP-8 were seen to be higher in MCL ≥3 than in MCL = 0 and MCL 1-2. The mean MMP-8 of controls, MCL 1-2, and MCL ≥3 were 131.34ng/ml, 230.14ng/ml, and 391.91ng/ml respectively. Multiple linear regression analysis with MMP-8 as the dependent variable revealed caries, buffer capacity and S. mutans count as significant variables. Using MCL as the dependent variable the only significant variable was MMP-8 levels. ConclusionsThe study suggests that subjects with caries have elevated MMP-8 levels compared with subjects with no carious lesions. There is also a positive correlation between the number of carious lesions and MMP-8 levels suggesting that MMP-8 plays an important role in the degradation of dentin and causes progression of caries. Key words:Caries, Dentin, Enzyme-linked Immunosorbent Assay, MMP-8.

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

AimThis 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. MethodsA 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. ResultsOverall, 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. ConclusionsSalivary 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.

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

To investigate the molecular forms of salivary matrix metalloproteinase (MMP)-8 in relation to periodontitis. 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, 1mM, oxidant) or amino phenyl mercuric acetate (APMA, 1mM). 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 20-27kDa 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 20-27kDa, in vitro, and salivary concentrations of T.denticola correlated significantly with salivary levels of fragmented MMP-8. 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.

Anti-rheumatic medication and salivary MMP-8, a biomarker for periodontal disease.

To investigate the impact of anti-rheumatic medications on salivary matrix metalloproteinase (MMP)-8 levels and MMP-8/TIMP (tissue inhibitor of MMPs)-1 ratio in patients with rheumatoid arthritis (RA) and periodontal findings during a 1-year follow-up. Salivary MMP-8 was measured by an immunofluorometric assay and TIMP-1 by an enzyme-linked immunosorbent assay of 53 patients with early untreated RA (ERA), naïve to synthetic disease modifying anti-rheumatic drugs (DMARDs), of 28 patients with chronic RA (CRA), candidates for biologic DMARDs and of 43 age- and sex-matched controls. Periodontal health was evaluated by bleeding on probing (BOP), pocket depth (PD), and periodontal inflammatory burden index (PIBI). Examinations were conducted twice for RA patients and once for controls. Salivary MMP-8 level and MMP-8/TIMP-1 ratio associated positively with PIBI in patients with chronic RA (MMP-8: p<0.001 at baseline, p=0.002 after follow-up; MMP-8/TIMP-1 ratio p<0.001, p=0.003, respectively) and in controls (MMP-8: p=0.010, MMP-8/TIMP-1 ratio: p=0.010). Salivary MMP-8 levels were highest at the early stage of RA. The used DMARDs, synthetic or biologic, did not affect salivary MMP-8 concentrations. The use of synthetic or biologic DMARDs did not affect salivary MMP-8 levels in RA patients regardless the duration of RA.

The potential of salivary biomarkers for predicting the sensitivity and monitoring the response to nonsurgical periodontal therapy: A preliminary assessment.

The response to nonsurgical periodontal treatment varied among patients. This study assessed the potential of salivary biomarkers for predicting the sensitivity and monitoring the response to nonsurgical periodontal therapy. This study recruited 34 participants with severe chronic periodontitis (the test group) and 20 participants without periodontal destruction in any teeth (the control group) from September 6, 2013 to August 25, 2017. Participants in the test group received nonsurgical periodontal therapy and were further divided into 2 subgroups of 17 low responders and 17 high responders, based on probing depth reduction. Clinical periodontal parameters were recorded, and saliva samples were harvested before and after nonsurgical periodontal therapy. Salivary biomarkers, including interleukin (IL)-1beta (IL-1β), IL-1 receptor antagonist (IL-1ra), IL-6, IL-8, platelet-derived growth factor-BB, vascular endothelial growth factor, MMP-8, MMP-9, C-reactive protein, and lactoferrin were analyzed. Compared with participants in the control group, participants in the test group had significantly greater periodontal pocket depth, clinical attachment level, and salivary IL-1β and MMP-8 levels, and all of these parameters were significantly reduced after nonsurgical periodontal therapy. The pretreatment levels of IL-1β, MMP-8, and lactoferrin were significantly higher in participants of the high-responder subgroup than participants of the low-responder subgroup.Based on the analysis from a dichotomous table, MMP-8 and lactoferrin showed odds ratios of 5.76, with 71% sensitivity and 71% specificity, and statistical significance (P=.02) for discriminating between the high- and low-responder subgroups. Salivary IL-1β and MMP-8 might be useful for diagnosing periodontitis and monitoring the recovery of periodontitis following nonsurgical periodontal therapy. MMP-8 and lactoferrin showed potential for predicting the sensitivity to the treatment.

Salivary matrix metalloproteinase (MMP)-8 as a biomarker for periodontitis: A PRISMA-compliant systematic review and meta-analysis.

Background:Salivary matrix metalloproteinase (MMP)-8 is currently considered to be one of the most promising biomarkers for early diagnosis of periodontitis, however, several recent studies showed conflicting results.Objective:To determine the salivary matrix metalloproteinase (MMP)-8 levels between periodontitis patients and healthy individuals, and to assess its diagnostic value in periodontitis.Methods:Literatures were searched on PubMed and Embase databases up to August 2017, for articles reporting salivary MMP-8 levels between periodontitis patients and health controls with the data of means ± standard deviation (SD). Methodological quality was assessed by the Newcastle Ottawa scale (NOS). Standard mean differences (SMDs), heterogeneity, and publication bias were assessed by Stata 13.0 software.Results:A total of 10 studies including 485 periodontitis patients and 379 healthy controls that met the preset inclusion criteria were included, the qualities of these studies were either good (n = 7) or moderate (n = 3). Eight studies showed salivary MMP-8 levels were higher in periodontitis patients compared with healthy controls (P < .05), while 2 studies showed opposite results (P > .05). The pooled SMD was 1.195 (95% CI: 0.720–1.670), with I2 of 89.3%, indicating high heterogeneity. Funnel plot showed publication bias existed.Conclusion:Our meta-analysis showed that salivary MMP-8 levels were significantly higher in periodontitis patients compared with healthy controls overall. Due to the heterogeneity and publication bias of included studies, further high quality studies are still needed to verify the conclusion.

Probiotic intervention influences the salivary levels of Matrix Metalloproteinase (MMP)-9 and Tissue Inhibitor of metalloproteinases (TIMP)-1 in healthy adults

ObjectiveTo study the effect of orally administered Bifidobacterium animalis subsp. lactis BB-12 and Lactobacillus rhamnosus GG on the salivary levels of Matrix Metalloproteinases (MMP)-8, MMP-9 and of Tissue Inhibitor of Metalloproteinases (TIMP)-1 in healthy adults. Furthermore, the correlations between MMP-8, MMP-9 and TIMP-1 and plaque and gingival indices, salivary mutans streptococci and lactobacilli counts, and stimulated saliva secretion rate were analysed. DesignThe salivary samples originated from a randomized controlled trial where healthy student volunteers consumed probiotic or placebo lozenges twice a day for four weeks. The saliva samples were collected and clinical parameters measured at the baseline and at the end of the original study. For this study, the salivary levels of MMP-8, MMP-9 and TIMP-1 were analysed with immunofluorometric assay (IFMA) and enzyme-linked immunosorbent assay (ELISA). ResultsIn the probiotic group (n=29), salivary MMP-9 levels increased (p<0.01) and TIMP-1 levels decreased (p<0.01) significantly during the intervention. Furthermore, MMP-9/TIMP-1 ratio differed significantly from the baseline level (p<0.01). These changes were not observed in the control group (n=31). In the whole data, salivary MMP-9 and gingival index correlated (r=0.260, p<0.05 at baseline and r=0.354, p<0.01 at the end of the study). Intergroup differences or correlations with other clinical parameters were not found. Probiotic consumption did not affect the saliva flow rate. ConclusionsIncreased MMP-9 and decreased TIMP-1 levels in saliva may indicate that probiotics have immunomodulatory effects in the oral cavity. Furthermore, increased salivary MMP-9 levels may be an indication of the defensive potential of matrix metalloproteinases.

Salivary Colony Stimulating Factor-1 and Interleukin-34 in Periodontal Disease.

Colony-stimulating factor (CSF)-1 and interleukin (IL)-34 are macrophage growth factors and regulators of osteoclastogenesis. Their potential involvement in periodontal disease is yet unknown. The aim of this study is to explore the presence of CSF-1 and IL-34 in whole saliva in relation to periodontal disease. Protocol validation was assessed in saliva of healthy donors (n = 21) by enzyme-linked immunosorbent assay. Salivary CSF-1, IL-34, and matrix metalloproteinase (MMP)-8, a biomarker candidate of periodontitis, were determined in 48 patients (29 patients with periodontitis, 12 with gingivitis, and seven healthy patients) and related to the following clinical periodontal parameters: bleeding on probing, probing depth, clinical attachment loss, and plaque index. An additional separate group of patients with gingivitis (n = 21) and some of the patients with periodontitis (n = 11) were subjected to non-surgical periodontal treatment, whereupon changes in salivary CSF-1, IL-34, and MMP-8 levels were determined and related to periodontal outcome. Patients with periodontitis displayed higher CSF-1 and MMP-8 levels in saliva compared with healthy patients, and IL-34 levels were lower. A higher CSF-1/IL-34 ratio was observed in patients with periodontitis compared with healthy patients. There was a positive correlation between CSF-1 and MMP-8, which both correlated negatively to IL-34, in patients with gingivitis and periodontitis. Clinical periodontal parameters correlated positively with CSF-1, MMP-8, and with the CSF-1/IL-34 ratio, and negatively with IL-34 in patients with periodontitis. After treatment CSF-1 and MMP-8 levels decreased together with observed clinical improvement in patients with gingivitis. CSF-1 and IL-34 are present in saliva and seem to have complementary roles in periodontal disease: IL-34 in steady-state and CSF-1 in inflammation.

Decreased salivary matrix metalloproteinase-8 reflecting a defensive potential in juvenile parotitis

ObjectiveMatrix metalloproteinases MMP-2 and MMP-9 have been associated with juvenile parotitis. However, the role of MMP-8 has not been addressed previously. This work focuses on salivary MMP-8 and -9 levels in juvenile parotitis. MethodsDuring a five-year period at Helsinki University Hospital, a tertiary care hospital, 41 patients aged 17 or under, were identified as having parotitis; from 36 of these patients, saliva samples were collected for MMP-8 IFMA (time-resolved immunofluorometric assay) analyses. Control saliva samples were collected from 34 age- and gender-matched children admitted for an elective surgery who had no history of parotitis. For comparison, salivary levels of MMP-9, tissue inhibitor of matrix metalloproteinase (TIMP-1), MMP-8/TIMP-1 ratio, human neutrophil elastase (HNE), and myeloperoxidase (MPO) were analyzed by ELISA. Additionally, salivary MMP-8 levels were compared to historical saliva samples from 18 adult gingivitis patients as well as to 10 healthy adult controls. ResultsThe median (25%, 75% percentile) MMP-8 concentration in saliva of parotitis patients was significantly lower than MMP-8 concentration in saliva of their controls [50.4ng/ml (37.5, 72.9) vs. 148.5ng/ml (101.2, 178.5) p<0.0001] and lower than in patients with gingivitis [347.9ng/ml (242.6, 383.2) p<0.0001] or healthy adult controls [257.2ng/ml (164.9, 320.7) p<0.0001]. The MMP-8/TIMP-1 ratio was lower than in controls [0.13 (0.05–0.02) vs. 0.3 (0.17–0.46) p<0.0001]. The median MMP-9 concentration in saliva of parotitis patients was significantly higher than in controls [143.9ng/m (68.8–189.0) vs. 34.9ng/ml (16.3–87.6) p<0.0001]. Neither HNE, MPO, nor TIMP-1 alone separated the patients from the control groups. ConclusionsMMP-9 was up-regulated in juvenile parotitis saliva, suggesting that MMP-9 may play a destructive role in juvenile parotitis, as others have suggested. The present novel findings reveal a decreased salivary MMP-8 concentration, suggesting that MMP-8 may reflect in juvenile parotitis down-regulated or anti-inflammatory immune characteristics.