Salivary MMP-8 Research Articles

Evaluating Salivary MMP-8 as a Biomarker for Periodontal Diseases: A Systematic Review and Meta-Analysis

Evaluating Salivary MMP-8 as a Biomarker for Periodontal Diseases: A Systematic Review and Meta-Analysis

Salivary and serum inflammatory biomarkers during periodontitis progression and after treatment.

To identify serum- and salivary-derived inflammatory biomarkers of periodontitis progression and determine their response to non-surgical treatment. Periodontally healthy (H; n = 113) and periodontitis patients (P; n = 302) were monitored bi-monthly for 1 year without therapy. Periodontitis patients were re-examined 6 months after non-surgical periodontal therapy (NSPT). Participants were classified according to disease progression: P0 (no sites progressed; P1: 1-2 sites progressed; P2: 3 or more sites progressed). Ten salivary and five serum biomarkers were measured using Luminex. Log-transformed levels were compared over time according to baseline diagnosis, progression trajectory and after NSPT. Significant differences were sought using linear mixed models. P2 presented higher levels (p < .05) of salivary IFNγ, IL-6, VEGF, IL-1β, MMP-8, IL-10 and OPG over time. Serum analytes were not associated with progression. NSPT led to clinical improvement and significant reduction of IFNγ, IL-6, IL-8, IL-1β, MMP-8, IL-10, OPG and MMP-9 in saliva and of CRP, MMP-8, MMP-9 and MPO in serum. Periodontitis progression results from a sustained pro-inflammatory milieu that is reflected in salivary biomarkers, but less so in serum, likely because of the limited amount of progression per patient. NSPT can significantly decrease the levels of several salivary analytes.

Microbiological and Salivary Biomarkers Successfully Predict Site-Specific and Whole-Mouth Outcomes of Nonsurgical Periodontal Treatment.

Background/Objectives: Nonsurgical periodontal treatment (NSPT) is the gold-standard technique for treating periodontitis. However, an individual's susceptibility or the inadequate removal of subgingival biofilms could lead to unfavorable responses to NSPT. This study aimed to assess the potential of salivary and microbiological biomarkers in predicting the site-specific and whole-mouth outcomes of NSPT. Methods: A total of 68 periodontitis patients exhibiting 1111 periodontal pockets 4 to 6 mm in depth completed the active phase of periodontal treatment. Clinical periodontal parameters, saliva, and subgingival biofilm samples were collected from each patient at baseline and three months after NSPT. A quantitative PCR assay was used to detect the presence of Fusobaterium nucleatum and Porphyromonas gingivalis in the biofilm samples. Salivary biomarkers including matrix metalloproteinase (MMP)-9, glutathione S-transferase (GST), and Annexin-1 were assayed both qualitatively (Western blot analysis) and quantitively (ELISA). Results: NSPT yielded significant improvements in all clinical parameters, including a reduction in bacterial load and decreased levels of MMP-9 together with increased concentrations of GST and Annexin-1. The binary logistic regression suggested that the overall accuracy of P. gingivalis identification, probing pocket depth, and interproximal sites was 71.1% in predicting successful site-specific outcomes. The salivary biomarker model yielded an overall accuracy of 79.4% in predicting whole-mouth outcomes following NSPT. Conclusions: At baseline, the presence of shallow periodontal pockets at interdental locations with a lower abundance of P. gingivalis is predictive of a favorable response to NSPT at the site level. Decreased salivary MMP-9 associated with increased GST and Annexin-1 levels can predict successful whole-mouth outcomes following NSPT.

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.

Can nano-fat injection in patients with tempromandibular disorder alters salivary matrix metalloproteinases 2 and 9?

Temporomandibular disorder (TMD) is a musculoskeletal condition that affects temporomandibular joint, causing pain and dysfunction in the jaw area, jeopardizing the ability to eat and even sleep comfortably. A key factor in the pathogenesis of TMD is the enhanced breakdown of extracellular matrix components, such as collagen and elastin. This breakdown is mediated by enzymes known as matrix metalloproteinases (MMPs), specifically MMP2 and MMP9. Elevated expression of MMP2 and/ or MMP9 may be involved in the pathophysiology of TMD. Methodology: Stimulated saliva samples were obtained from Thirty-two TMD patients. MMPs in collected samples were analyzed by ELISA. Results: Three months after nano-fat injection, Means of MMP2 and MMP9 were significantly decreased compared to that before procedure (139.59 versus 128.46 ng/ml, P= 0.003; and 545.37 versus 469.09 ng/ml, P= 0.001 respectively). Conclusion: this study provides evidence for a significant reduction in salivary MMP2 and MMP9 levels among TMD patients following nano-fat injection therapy. These findings suggest that nano-fat injections may have therapeutic potential for managing TMD by modulating ECM remodeling processes through their effects on these enzymes.

A disposable immunosensor for the detection of salivary MMP-8 as biomarker of periodontitis

This work describes the development of a novel voltammetric immunosensor for the detection of salivary MMP-8 at the point-of-care. The electrochemical platform was based on a graphene (GPH) screen-printed electrode (SPE) functionalized by gold-nanospheres (AuNSs) and antibodies against MMP-8 protein (anti-MMP-8). The functionalization with anti-MMP-8 was realized by using 11-mercaptoundecanoic acid (11-MUA), thanks to its ability to give strong sulfur bonds with its –SH end, and to cross-link the –NH2 groups of the antibody molecule with the other –COOH end, using the traditional EDC-NHS method. The voltammetric sensor showed good performances with a linear range of 2.5–300 ng mL−1, a LOD value of 1.0 ± 0.1 ng mL−1 and a sensitivity of 0.05 µA mL cm−2 ng−1. Moreover, the proposed immunosensor was tested in real saliva samples, showing comparable results to those obtained with the conventional ELISA method. The biosensor was single-use and cost-effective and required a small quantity of test medium and a short preparation time, representing a very attractive biosensor for MMP-8 detection in human saliva.

The assessment of MMP-8 among different stages of periodontitis in the Iraqi population

This research aims to explore the potential of MMP-8 as a biomarker for diagnosing periodontitis using the latest classification system for this condition. This study enrolled 63 patients with periodontitis and classified them into stage II and stage III periodontitis groups. Additionally, 18 healthy/intact periodontium individuals were included as a control group. Clinical periodontal parameters were assessed, and 3 ml of whole unstimulated saliva was collected from each participant. The results revealed that both PLI (Plaque Index) and BOP (Bleeding on Probing) were considerably elevated in both stages of periodontitis compared to the healthy/control group. There were no statistical differences between periodontitis stages for PLI, BOP, and PPD (Probing Pocket Depth); however, Clinical Attachment Level (CAL) showed a substantial difference across the different stages of periodontitis. The concentrations of MMP-8 were substantially higher in both stages than in the control group, with a significant difference between the periodontitis stages, as the mean concentration was higher in stage II than in stage III. Furthermore, a significant positive correlation was observed between aMMP-8 levels and all periodontal indices. ROC analysis showed that salivary MMP-8 had good diagnostic accuracy for differentiating between periodontal health and periodontitis. However, salivary MMP-8 was unable to distinguish between periodontitis stages.

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.

Effect of Locally Injectable Platelet-Rich Plasma as an Adjunct to Scaling and Root Planing on Salivary MMP-8 Level in Periodontitis Patients

Objective: To assess the effect of platelet-rich plasma (PRP) local injection in the treatment of periodontitis, as an

Relation of salivary MMP-8 with oral submucous fibrosis and oral squamous cell carcinoma: a cross sectional analytical study

ObjectivesWe aim to evaluate salivary matrix metalloproteinases (MMP-8) levels in oral submucous fibrosis (OSF) and oral squamous cell carcinoma (OSCC) for the purpose of diagnosis at the early stage via...

Salivary Enzymatic Activity and Carious Experience in Children: A Cross-Sectional Study.

Salivary biomolecules are considered important modulators of the oral microflora, with a potential subsequent impact on dental health. The present study aimed to investigate the relationship between salivary enzymatic activity and carious experience in children. The carious experience of a sample of 22 school children was evaluated by calculating dmf/DMF indices, following WHO recommendations. Unstimulated whole saliva was collected, and salivary alpha-amylase levels, total protease activity, and matrix metalloproteinase levels (MMP-8 and MMP-9) were measured. The data were analyzed using parametric and nonparametric tests. Our findings revealed no significant relationship between the investigated salivary parameters and the carious experience in permanent teeth (DMFT/DMFS scores). Carious indices scores for primary teeth (dmft and dmfs) were positively associated with MMP-8 levels (r = 0.62, p = 0.004 and rs = 0.61, p = 0.006, respectively) and MMP-9 levels (r = 0.45, p = 0.05 and rs = 0.48, p = 0.039, respectively) and negatively associated with alpha-amylase levels (rs = −0.54, p = 0.017 and rs = −0.59, p = 0.006, respectively). Although with a marginal significance, PEK−054 levels positively correlated with dental caries, while for PFU−089, a negative correlation was observed. These results suggest that salivary alpha-amylase and MMP-8 and MMP-9 levels may be considered potential indicators of carious experience in children. Further studies with a prospective design are needed in order to elucidate the role of these biomolecules in caries development.

Salivary ACE2 and TMPRSS2 link to periodontal status and metabolic parameters

AbstractBackgroundPeriodontitis links extensively to various non‐communicable diseases such as diabetes and cardiovascular disease and most recently COVID‐19 complications. Two important proteins in humans, ACE2 and TMPRSS2, have been associated with various health problems and coronavirus infection. This study was to investigate the soluble ACE2 and TMPRSS2 in saliva and serum as well as their association with periodontal status and systemic conditions.MethodsThe demographic background, lifestyles, full‐mouth periodontal status and medical parameters in 139 subjects were examined and recorded. Saliva and serum samples were collected for determining the levels of ACE2, TMPRSS2 and MMP8.FindingsThe salivary levels of ACE2 increased with the severity and complexity of periodontitis and correlated positively with alveolar bone loss and salivary MMP8 as an inflammatory biomarker. While, the salivary levels of TMPRSS2 were negatively correlated with body mass index (BMI), cholesterol/high‐density lipoprotein (HDL) ratio, low‐density lipoprotein (LDL), salivary MMP8 and number of remaining teeth. No inter‐correlation existed among ACE2 and TMPRSS2 levels in both saliva and serum.ConclusionsThe present study demonstrated the disparate correlation of the soluble ACE2 and TMPRSS2 with periodontal and systemic parameters. Salivary ACE2 could differentiate periodontal health and severe periodontitis, while salivary TMPRSS2 prominently linked to the metabolic parameters of obesity and cardiovascular disease. Our findings imply the potential application of the biofluidic soluble form of SARS‐CoV‐2 entry proteins in assessing oral or systemic conditions and delivering appropriate healthcare.

The Role of Matrix Metalloproteinases (MMP-8, MMP-9, MMP-13) in Periodontal and Peri-Implant Pathological Processes.

Severe periodontitis, a destructive inflammatory disease of the supporting tissues of the teeth, ranks sixth in terms of global spread, affecting about 11% of the population. Metalloproteinases (MMPs) are extracellular matrix (ECM) macromolecules that are important in cellular development and morphogenesis, and they are capable of activating growth factors in their proximity, cell surface receptors, and adhesion molecules. MMPs are part of a major family of zinc-dependent endopeptidases, and their activity is modulated and regulated by certain inhibitors known as tissue metalloproteinase inhibitors (TIMPs). Because type I collagen is the major component of the periodontal extracellular matrix, special attention has been paid to the role of collagenases, especially MMP-8 and MMP-13 and gelatinases, MMP-2 and MMP-9, in periodontal diseases. In fact, MMP-8 (or collagenase 2) is currently one of the most promising biomarkers for periodontitis in oral fluids. Among them, salivary MMP-9 has been shown to be a more sensitive marker for periodontal inflammation during orthodontic treatment, which opens new perspectives in reducing periodontal hazards during such treatments. Both MMP-8 and MMP-9 are extremely valuable diagnostic tools in treating periodontitis, and future studies and healthcare policies should focus on implementing more accessible methods of chairside testing in order to reduce the prevalence of this disease.

Anti-Inflammatory Potential of Complex Extracts of Ligularia stenocephala Matsum. & Koidz. and Secale cereale L. Sprout in Chronic Gingivitis: In Vitro Investigation and Randomized Clinical Trial.

Complex extracts of Ligularia stenocephala Matsum. & Koidz. (LSE) and Secale cereale L. sprout (SCSE) (TEES-10®) were prepared. The purposes of the study were to evaluate anti-inflammatory activities of TEES-10® in vitro and to observe resolution of gingivitis in human with oral administration of TEES-10®. The effects of TEES-10® on normal periodontal ligament (PDL) cell viability, lipopolysaccharide (LPS) induced PDL cell viability and the changes of inflammatory mediator expression were evaluated in vitro. In the clinical trial, 150 mg of TEES-10® powder containing capsule was administered twice daily to the test group, while the control group administered placebos in a total 100 participants with gingivitis. Probing depth (PD), bleeding on probing (BOP), clinical attachment loss, gingival index (GI) and plaque index (PI) were measured at baseline and 4 weeks. Administering TEES-10® showed significant increase in PDL cell viability compared to administering LSE or SCSE alone. In addition, treating TEES-10® to LPS induced PDL cell significantly increased PDL cell viability compared to control. TEES-10® suppressed expression of NF-κB, p-ERK, ERK, COX-2, c-Fos and p-STAT and promoted expression of PPARγ in LPS induced PDL cells. In the clinical trial, significant improvement of GI and BOP was observed in the test group at 4 weeks. In addition, the number of patients diagnosed with gingivitis was significantly reduced in the test group at 4 weeks. Salivary MMP-8 and MMP-9 was also significantly decreased compared to placebo group. Within the limitations of this study, the TEES-10® would have an anti-inflammatory potential clinically in the chronic gingivitis patients.

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.

Matrix Metalloproteinases (MMPs) in skin and oral pathology - Premalignant Diseases, Spinocellular Carcinoma and Basocellular Carcinoma (markers).

Matrix Metalloproteinases (MMPs) in skin and oral pathology - Premalignant Diseases, Spinocellular Carcinoma and Basocellular Carcinoma (markers).

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.

Evaluation of salivary biomarkers for the diagnosis of periodontitis

BackgroundSalivary interleukin (IL)-1β, matrix metalloproteinase (MMP)-8, pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and Porphyromonas gingivalis (Pg) are related to periodontitis. This study aimed to investigate the diagnostic potential of these biomarkers and to build a prediction panel for diagnosing periodontal disease.MethodsA total of 80 participants were enrolled in a cross-sectional study and divided into healthy (n = 25), gingivitis (n = 24), and periodontitis (n = 31) groups based on their periodontal exam results. A full mouth periodontal examination was performed and unstimulated saliva was collected. Salivary IL-1β, MMP-8, ICTP, and Pg were assessed using enzyme-linked immunosorbent assay (ELISA) and quantitative real time PCR (qPCR). Their potentials for diagnosing periodontal disease were analyzed and combined prediction panels of periodontal disease were evaluated.ResultsAs a single marker, IL-1β showed the best diagnostic value of the four markers evaluated and exhibited an area under the curve (AUC) value of 0.88 with 90% sensitivity and 76% specificity for discriminating periodontitis subjects from healthy subjects, an AUC value of 0.80 with 83% sensitivity and 76% specificity for discriminating gingivitis subjects from healthy subjects and an AUC value of 0.66 with 68% sensitivity and 64% specificity for differentiating periodontitis subjects from gingivitis subjects. The combination of IL-1β, ICTP, and Pg exhibited the highest efficacy for discriminating periodontitis subjects from healthy subjects (AUC = 0.94) and gingivitis subjects (AUC = 0.77). The combination of IL-1β and MMP-8 exhibited the best ability to discriminate gingivitis from healthy subjects (AUC = 0.84).ConclusionsSalivary IL-1β, MMP-8, ICTP, and Pg showed significant effectiveness for diagnosing periodontal disease. The combination of IL-1β, ICTP, and Pg can be used to discriminate periodontitis subjects from healthy subjects and gingivitis subjects, and the combination of IL-1β and MMP-8 can be used to discriminate gingivitis subjects from healthy subjects.

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.

Diagnostic and prognostic ability of salivary MMP-9 for oral squamous cell carcinoma: A pre-/post-surgery case and matched control study.

Over 90% of oral cancers are oral squamous cell carcinoma (OSCC). Hitherto, early detection marker for OSCC has not been available. Hence, this study aimed to evaluate the diagnostic and prognostic ability of salivary matrix-metalloproteinase-9 (MMP-9) and 8-hydroxydeoxyguanosine (8-OHdG) for OSCC. Total of 318 participants with 106 cases and 212 controls were included: OSCC cases were from Seoul National University Dental Hospital and age, sex, and smoking matched controls were from Yangpyeong cohort. Unstimulated saliva was collected to determine MMP-9 and 8-OHdG using sensitive enzyme-linked immunosorbent assay. Multivariable linear regression and analysis of covariance (ANCOVA) were applied to evaluate the adjusted association of markers with OSCC. Wilcoxon sign rank sum test and Friedman test for median were applied to evaluate follow-up level of MMP-9 after surgery. Receiver operating characteristic curve was obtained for diagnostic ability. Salivary MMP-9 was associated with OSCC (ANCOVA and multivariable linear regression, p<0.05), while 8-OHdG was not. The diagnostic ability of MMP-9 was area under curve of 0.96 (100% specificity and 89.6% sensitivity, p<0.001). MMP-9 decreased dramatically after tumor surgery (p<0.05). Salivary MMP-9 could be a critical diagnostic and prognostic marker for OSCC.