Salivary Matrix Metalloproteinases Research Articles

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.

Matrix metalloproteinases system profile analysis and their endogenous inhibitors in children with periodontal diseases and various dysplasia phenotypes

Relevance. The search and development of modern non-invasive methods for early periodontal disease detection are of scientific and practical value for a personalized approach to disease course prognosis and explaining the choice of treatment tactics. Morphological immaturity, high intensity of anabolic processes, functional failure of neurohumoral, endocrine and immunological defence systems combined with an imbalance between the synthesis and degradation of extracellular matrix components in children with undifferentiated connective tissue disease (UCTD) significantly increases the risk of developing periodontal diseases. The available data on the activity of salivary matrix metalloproteinases (MMPs), which play a leading role in regulating connective tissue protein metabolism and bone remodelling mechanisms in children with UCTD of various degrees, are scarce and require further study.Purpose. The study aimed to explain the clinical, diagnostic and prognostic value of MMPs as markers of inflammatory periodontal diseases in children with UC TD and dysplastic disorders of various se verity.Material and methods. The study included 67 children with UCTD (main group) and 34 children of health groups I and II (comparison group) aged 12-17. The UCTD severity was established according to the diagnostic criteria by L. N. Abbakumova (2006) and a scale for assessing the significance of phenotypic and visceral signs. The main group was divided into two subgroups: Subgroup 1 (n = 38) – children with mild and moderate UCTD; Subgroup 2 (n=29) – children with severe UCTD. The studied groups had their periodontal status assessed, as well as the concentration of MMP-1, MMP-2, MMP-8, MMP-9 and their tissue inhibitors (TIMP-1, TIMP-2) in the oral fluid identified using the enzyme immunoassay, along with calculation done for the MMP ⁄ TIMP coefficients that set a balance between the degradation and synthesis of collagen.Results. The children with phenotypic signs of UCTD in the oral fluid appeared to show a statistically significant increase in the MMP-1, MMP-2, MMP-8, and MMP-9 levels and an imbalanced ratio in MMP-1⁄TIMP-1, MMP- 2⁄TIMP-2, MMP-8⁄TIMP-1, MMP-9⁄TIMP-1, compared with health groups I, II. An increase in the MMP-1, MMP-2, and MMP-8 concentrations, along with dominating expression of MMP-9 over TIMP-1 in the oral fluid of children of Subgroup 2, causes an increase in intensity and prevalence of periodontal diseases compared to the patients in Sub-group 1 and comparison group.Conclusion. Thus, when children with UCTD don’t demonstrate an increase in specific tissue inhibitors TIMP-1 and TIMP-2 in their oral fluid, along with an increase in the levels of the respective matrixins is the key pathogenetic factor in the degradation of extracellular matrix proteins, which causes a depressing impact on the proliferative activity in the periodontal set of tissues.

Effect of 38% Silver Diamine Fluoride on Salivary Matrix Metalloproteinase-9 Levels in Children with Early Childhood Caries: A Clinical Study.

Early childhood caries is a major oral health problem in most industrialized countries, affecting the overall quality of life of children. It is caused by the action of bacterial acids on the enamel surface thereby demineralizing it and progressively destroying the tooth. It presents initially as smooth-surface carious lesions affecting the primary maxillary incisors. With the advancement of the lesion, decay progresses further to involve other primary teeth as well and if not treated early, the caries may involve the pulp leading to irreversible pulpitis. Matrix metalloproteinases (MMPs) are a group of endopeptidases that degrade almost all the proteins of the extracellular matrix (ECM). Among the different types of MMP, MMP-9 (gelatinase B) is one of the chief MMPs responsible for the breakdown of the organic matrix. Traces of MMP-9 can be found in the human carious lesions, saliva, and gingival crevicular fluid. They are activated by the release of acids by cariogenic bacteria and once activated they are able to digest demineralized dentin matrix. Thus, host-derived MMPs, which are activated by bacterial acids have a crucial role in the destruction of dentine by caries. Thus, this study was undertaken to investigate the effect of 38% silver diamine fluoride (SDF) solution on MMP-9 levels. This clinical trial investigated the MMP-9 levels before and after the application of 38% SDF in children with early childhood caries. About 15 children were selected and were subjected to clinical and radiographic assessment before the commencement of the procedure. After the collection of saliva, the teeth with carious lesions were isolated and SDF was applied. Saliva samples were again collected after 1, 3, and 6 months postapplication of SDF. The collected saliva samples were then analyzed for their MMP-9 levels using a human salivary enzyme-linked immunosorbent assay (ELISA) kit. Finally, the data obtained were subjected to statistical analysis by repeated measures of analysis of variance (ANOVA). The MMP-9 levels were found to be gradually increasing postapplication of 38% SDF and were significantly higher after 6 months and the highest mean difference in the MMP-9 levels was observed between baseline and 6th-month follow-up. Also, no new carious lesion appeared in the teeth during the experimental time period of 6 months and the decayed, extraction needed, filled teeth (deft) scores remained the same. Bora P, Saxena A, Goswami M. Effect of 38% Silver Diamine Fluoride on Salivary Matrix Metalloproteinase-9 Levels in Children with Early Childhood Caries: A Clinical Study. Int J Clin Pediatr Dent 2023;16(S-1):S51-S56.

Salivary matrix metalloproteinase-9 (MMP-9) as a biomarker of periodontitis in pregnant patients with diabetes.

Pregnancy and diabetes increase the risk of developing pathological conditions in the periodontium. Salivary biomarkers, such as matrix metalloproteinase-9 (MMP-9), as well as antioxidants can be used as diagnostic indicators in monitoring periodontitis. The aim of the study was to assess the periodontal status of pregnant women with regard to the presence of diabetes. In addition, we aimed to assess antioxidant activity and the level of MMP-9 in saliva in order to establish the optimal noninvasive determinants of periodontitis. The study included 104 pregnant women: 35 patients had gestational diabetes mellitus (GDM); 30 patients had type 1 diabetes (T1D); and 39 patients did not have diabetes (the control group). The physical examination included the assessment of the approximal plaque index (API), the gingival index (GI), bleeding on probing (BOP), the probing pocket depth (PPD), and clinical attachment loss (CAL). In the saliva study, MMP-9 concentration as well as the ferric reducing ability of plasma (FRAP), and the activity of superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GPX) were measured. The pregnant patients with GDM and T1D had higher GI, BOP, PPD, and CAL scores than the control women (p < 0.0001, p = 0.0040, p = 0.0100, p = 0.0030, and p < 0.0001, p < 0.0009, p < 0.0001, p < 0.0001, respectively). The T1D patients had higher API scores as compared to the control women (p = 0.0010). The patients with periodontitis had higher salivary MMP-9 levels than the patients without periodontitis (p = 0.0001). The salivary antioxidant levels and activity were comparable among the study groups. The determinants of periodontitis (p < 0.0001) were MMP-9 concentration (p = 0.0008) and oral hygiene (p = 0.0001). The concentration of MMP-9 was also a useful determiner of the presence of periodontitis (p < 0.0001). In the pregnant women with diabetes, we observed worse gingival conditions, deeper periodontal pockets and greater attachment loss in comparison with the women from the control group. The concentration of MMP-9 in saliva is a good predictor of periodontitis and might be a useful tool for diagnosing periodontitis.

Evaluation of the Salivary Matrix Metalloproteinase-9 in Women With Polycystic Ovaries Syndrome and Gingival Inflammation: A Case-Control Study.

Background Polycystic ovary syndrome (PCOS) is an endocrine disease of women of reproductive age that impacts their oral and systemic well-being. This study aimed to compare the gingival inflammation indices and matrix metalloproteinase-9 (MMP-9) of non-obese women with PCOS. Materials and methods This is a case-control study in which 78 women were referred to the Babol Clinic Hospital in Northern Iran between 2018 and 2019. They were divided into three groups:26 women with PCOS and gingivitis, 26 women with PCOS with no gingivitis, and 26 women with no PCOS and no gingivitis as a control group. After recording the anthropometric and demographic variables, fasting saliva samples were taken from all participants before any periodontal intervention. These samples were transferred to Babol Molecular Cell Research Center under highly guaranteed cold-chain conditions to measure the serum levels of MMP-9. Periodontal status was evaluated for Gingival Index (GI), Plaque Index (PI), and Bleeding on Probing (BOP). Analysis of variance was used to compare the mean results for these indices. The significance level was considered when p ≤ 0.05. Results All the gingival indices were significantly higher for women with PCOS with gingivitis compared to the results for women from the other two groups. Similarly, women with PCOS showed high salivary MMP-9 levels but were within the normal reference ranges. Conclusion The gingival indices (GI, PI, and BOP) and salivary MMP-9 are higher in women with PCOS, regardless of the gingival status.

Determination and correlation of matrix metalloproteases profile and total antioxidant capacity in severe early childhood caries children - A randomized clinical trial.

Matrix metalloproteinases (MMPs) are a multigene family that belongs to the metalloproteinase class of endopeptides, responsible for the remodeling and degeneration of extracellular matrix molecules. MMPs are collectively called Matrixins are known to participate in tooth development and dentin-caries progression. Total antioxidant capacity (TAC) is the measure of the amount of free radicals scavenged by a test solution, being used to evaluate the antioxidant capacity of biological samples. Oxidative stress can affect the initiation and progression of many inflammatory and infectious diseases such as dental caries. Early childhood caries (ECC) is a serious public health problem that adversely affects children's physical and mental health. The study aims to investigate and correlate the presence of MMPs and TAC in saliva of children with ECC. The present study was done on 50 children aged 3-6 years with severe ECC. Unstimulated, whole saliva samples were collected and stored and all 50 samples were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis to determine MMPs and were subjected to spectrometry to assess the TAC of saliva. The samples with the presence of MMPs and increased TAC values were subjected to liquid chromatography-mass spectrometry to check the correlation of MMPs and TAC in ECC. TAC was 0.81 ± 0.14 mmol/l in the caries-active group and 0.15 ± 0.05 mmol/l in the caries-free group and was statistically significant at P < 0.001. MMP level in the caries-active group was 715.75 ± 102.42 μg/ml, whereas, in the caries-free group, it was 250.89 ± 86.51 μg/ml and was statistically significant at P < 0.001. The salivary MMP and TAC levels showed a significant positive moderate correlation with caries scores in the caries-active group and the finding was statistically significant at P < 0.001. From our results, it can be concluded that the both MMPs and TAC levels were high in caries active group than in the caries-free group. The salivary MMPs showed a moderate positive correlation with TAC in the ECC group. In age-wise comparison, the mean MMP levels in the caries active group were higher in children between 3 and 4 years than in 5-6 years. In the caries-free group, the mean MMP level was similar in both the age groups.

The Use of Salivary Levels of Matrix Metalloproteinases as an Adjuvant Method in the Early Diagnosis of Oral Squamous Cell Carcinoma: A Narrative Literature Review.

Oral squamous cell carcinoma (OSCC) is an aggressive malignancy with increased mortality, in which the early diagnosis is the most important step in increasing patients' survival rate. Extensive research has evaluated the role of saliva as a source of diagnostic biomarkers, among which matrix metalloproteinases (MMPs) have shown a valuable potential for detecting even early stages of OSCC. The aim of this review was to present recent clinical data regarding the significance of salivary MMPs in the detection of early malignant transformation of the oral mucosa. A narrative review was conducted on articles published in PubMed, Cochrane Library, Web of Science, EBSCO and SciELO databases, using specific terms. Our search revealed that MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, MMP-12 and MMP-13 had significantly higher levels in saliva from patients with OSCC compared to controls. However, the strength of evidence is limited, as most information regarding their use as adjuvant diagnostic tools for OSCC comes from studies with a low number of participants, variable methodologies for saliva sampling and diagnostic assays, and insufficient adjustment for all covariates. MMP-1, MMP-3 and MMP-9 were considered the most promising candidates for salivary diagnosis of OSCC, but larger studies are needed in order to validate their clinical application.

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...

Determination of the Accuracy of Salivary Biomarkers for Periodontal Diagnosis.

Background: We aimed to investigate the accuracy of salivary matrix metalloproteinases (MMP)-8 and -9, and tissue inhibitor of metalloproteinase (TIMP)-1 in diagnosing periodontitis and in distinguishing periodontitis stages (S)1 to S3. Methods: This study was a case–control study that included patients with periodontitis S1 to S3 and subjects with healthy periodontia (controls). Saliva was collected, and then, clinical parameters were recorded, including plaque index, bleeding on probing, probing pocket depth, and clinical attachment level. Diagnosis was confirmed by assessing the alveolar bone level using radiography. Salivary biomarkers were assayed using an enzyme-linked immunosorbent assay. Results: A total of 45 patients (15 for each stage) and 18 healthy subjects as controls were included. The levels of all salivary biomarkers and clinical parameters were significantly higher in periodontitis subjects than in the controls. The ROC curve showed that MMP-8, MMP-9, TIMP-1, MMP-8/TIMP-1, and MMP-9/TIMP-1 had statistically significant diagnostic accuracy, with areas under the curve (AUCs) of 0.892, 0.844, 0.920, 0.986, and 1.000, respectively, when distinguishing periodontitis from the controls. Similarly, these biomarkers showed significant diagnostic accuracy in the differentiation of S1 periodontitis from the controls (AUC range from 0.902 to 1.000). Conclusions: This study suggested that salivary biomarkers exhibited high diagnostic accuracy in distinguishing periodontal health from periodontitis in general as well as S1 periodontitis. Furthermore, TIMP-1 could differentiate S1 from S3.

Potential of Salivary Matrix Metalloproteinase 9 to Discriminate Periodontal health and disease

Periodontitis is a chronic inflammatory disease resulted from aggravated immune response to a dysbiotic subgingival microbiota of a susceptible host. Consequences of periodontitis are not only limited to the devastating effect on the oral cavity but extends to affect general health of the individual and also exerts economic burdens on the health systems worldwide. Despite these serious outcomes of periodontitis; however, they are avoidable by early diagnosis with proper preventive measures or non-invasive interventions at earlier stages of the disease. Clinically, diagnosis of periodontitis could be overlooked due to certain limitations of the conventional diagnostic methods such as periodontal charting and radiographs. Utilization of readily available biomarkers in the oral biofluids represents a potential opportunity to overcome these issues. This topic received great attention in the last decades and one of these biomarkers is matrix metalloproteinase 9 which is highlighted in this review as one of the candidates that can be used for diagnosis of periodontal diseases

Changes in salivary matrix metalloproteinase-3, -8, and -9 concentrations after 6 weeks of non-surgical periodontal therapy

BackgroundStudies using salivary inflammatory biomarkers for diagnosing and monitoring the progression of periodontal disease have garnered increased attention in recent years. The present study aimed to identify changes in clinical parameters and concentrations of salivary matrix metalloproteinases (MMPs) following 6 weeks of non-surgical periodontal therapy (NSPT).MethodsA 6-week NSPT program was applied to 51 adults aged ≥ 20 years. The program involved scaling, root planing, and professional toothbrushing for healthy participants and those with periodontal disease. Patients with periodontal disease underwent professional toothbrushing during all three visits. Periodontal pocket depth (PD) and gingival bleeding were assessed at week 0, week 3, and week 6, and saliva samples were collected to measure the concentrations of MMP-3, -8, and -9.ResultsAll clinical parameters were improved in the periodontal disease groups following the NSPT course. Compared with healthy participants, the patients with periodontal disease showed increased concentrations of salivary MMP-3, -8, and -9. During the 6-week program, patients with periodontal disease also showed significant reductions in PD and gingival bleeding during the third week; no significant reduction was found during the sixth week. Significant reductions in the concentrations of salivary MMP-3, -8, and -9 were also noted in the periodontal disease group at week 3. The sensitivity and specificity of MMP-3 for predicting periodontitis were 81.8% and 55.5%, respectively.ConclusionThe present study found that NSPT resulted in reductions of salivary MMP-3, -8, and -9, and identified the potential of MMP-3 as a biomarker in the diagnosis of periodontal disease. These findings may serve as foundational data for future studies into the development of diagnostic kits for periodontal disease.

Salivary MMP-9 Levels in Chronic Periodontitis Patients with Type-II Diabetes Mellitus.

Chronic periodontitis and diabetes mellitus share a two-way relationship, the common factor being the inflammatory-mediated pathway, and various cytokines are released during this inflammatory cascade, one of which being matrix metalloproteinase-9. The aim of this study was to identify whether the levels of matrix metalloproteinase-9 are increased due to type-II diabetes mellitus in chronic periodontitis patients. It was an observational, analytical, case-control study. Thirty subjects were recruited in the test group, who were suffering from type-II diabetes mellitus and chronic periodontitis, and 30 subjects in the control group, who were subjects with chronic periodontitis but systemically healthy. Periodontal parameters, including the plaque score, gingival bleeding index, probing pocket depth and clinical attachment level of the subjects, were measured, saliva samples of all of the subjects were collected and salivary matrix metalloproteinase-9 levels were analyzed by an enzyme-linked immunosorbent assay (ELISA) technique. The statistical analysis was performed using SPSS 24. Overall, the matrix metalloproteinase-9 levels of the diabetic patients with chronic periodontitis were increased almost twofold (156.95 ± 29.80 ng/mL) compared to the levels in the controls (74.96 ± 6.32 ng/mL) (p < 0.001). Similarly, the periodontal parameters were far worse in diabetics with chronic periodontitis compared to the controls. The average gingivitis score for the test subjects was 78.45 ± 8.93%), compared to 29.32 ± 12.96% in the controls (p < 0.001). The mean probing pocket depth for the test group was 5.39 ± 0.60 mm, and, for the control group, it was 4.35 ± 0.31 mm (p < 0.001). For the test subjects, the average clinical attachment level was 5.86 ± 0.58 mm, and it was 4.66 ± 0.32 mm for the controls (p < 0.001). It was ascertained that there is a two-fold increase in the levels of salivary matrix metalloproteinase-9 in the test group compared to the control group. In addition, the level of periodontal apparatus destruction was greater in the test group. This proved that type-II diabetes mellitus influences the levels of matrix metalloproteinase-9 in humans and elevates them, causing further periodontal destruction.

Analytical Study Of Salivary Mmp-12 Expression In Oral Submucous Fibrosis.

Oral submucous fibrosis (OSF) is majorly a pathology pertaining to Asian population, reported most in Pakistan, India, Nepal, Bangladesh, and Taiwan. Equilibrium existing between Matrix metalloproteinases (MMP) & tissue inhibitors of matrix metalloproteinases is imperative for the normal integrity of connective tissues. However, this mechanism is disturbed in the presence of OSF, resulting in an increase in the extracellular matrix. It is an analytical study including two groups with a total of 60 participants. The first group consists of 30 healthy participants and the other group consists of 30 patients presenting with oral submucous fibrosis. Collected samples of saliva were stored at -80 °C after centrifugation. For ELISA investigation, the procedure was performed as per manufacturer's instruction. Salivary matrix metalloproteinases- 12 concentration was estimated with the help of a standard curve. Data was analysed using SPSS 23. Mann Whitney test was applied to determine the difference existing in Matrix metalloproteinases- 12 levels between healthy and oral submucous fibrosis participants. p-value <0.05 was contemplated as significant. Statistical investigation indicated significant difference in Matrix metalloproteinases- 12 levels between Oral submucous fibrosis and healthy group (p<0.05). Saliva samples obtained from oral submucous fibrosis patients demonstrated raised concentrations of Matrix metalloproteinases- 12 as compared to healthy participants. Our study demonstrates significant upsurge in Matrix metalloproteinases- 12 expression in samples of saliva obtained from oral submucous fibrosis patients as compared to healthy individuals. Therefore, salivary Matrix metalloproteinases- 12 could serve as a useful diagnostic marker for OSF.

Alliance of Matrix Metalloproteinase-9 Promoter-1562C/T Polymorphism and Metalloproteinase-9 Saliva Concentration of Iraqi Patients with Chronic Periodontitis

Matrix metalloproteinases (MMPs) are key enzymes responsible for matrix degradation, derived frompolymorphonuclear leukocytes, during the early stages of periodontitis. There is plenty of evidencefor the role of matrix metalloproteinases in the destructive processes of periodontal disease as a viabletarget in early diagnosis and chemotherapeutic approach. The aim of this study was to determine thelevels of salivary matrix metalloproteinase-9 (MMP-9) in patients with periodontitis and healthycontrols and the role of gene polymorphisms in the aetiology of the disease. Levels of MMP-9 insaliva was determined by enzyme linked immune sorbent assay (ELISA) technique in healthy subjectswithout any periodontal disease (n = 45) and in the patients with diagnosed periodontitis (n = 45).Gene Amplification, gel electrophoresis and genotyping were also carried out on MMP-9 gene. TheMMP-9-1562C/T appeared in three genotypes: CC, CT and TT, allele specific gene polymorphism wasamplified by PCR technique. The distribution of different genotypes in patients and controls for each ofMMP-9-1562C/T polymorphism was in a good accordance with Hardy-Weinberg equilibrium (HWE).Genotypes in both dominant and recessive models were non-significantly associated with periodontitis.Significantly higher salivary MMP-9 was observed in cases of periodontitis compared to healthy adults(p = 0.043). Salivary MMP-9 may serve as a biomarker of periodontal disease monitoring and aid inthe early detection of periodontitis.

Clinical and Immunological Efficacy of Mangosteen and Propolis Extracted Complex in Patients with Gingivitis: A Multi-Centered Randomized Controlled Clinical Trial.

Background: Mangosteen and propolis extracts (MAEC) have been potential therapeutic agents known to exhibit powerful antioxidant and anti-inflammatory properties. The aim of the current study was to evaluate the clinical and immunological efficacy of MAEC as well as safety and patient-reported outcomes (PROMs) on gingivitis and incipient periodontitis. Methods: This study was performed on 104 patients diagnosed with gingivitis or incipient periodontitis. At baseline, the participants were randomly allocated to either the test group, with daily intake of a single capsule containing 194 mg of MAEC for eight weeks, or control group, with placebo. Clinical periodontal evaluation and immunological parameters from saliva and gingival sulcular fluid were assessed at baseline, four, and eight weeks. Individual PROMs were assessed by OHIP-14 questionnaires. Results: There was a significant difference of modified gingival index at four and eight weeks between the test and control groups. In the test group, crevicular interleukin (IL)-6 was reduced, and the salivary matrix metalloproteinase (MMP)-9 was increased after eight weeks. PROMs were improved up to four weeks compared to placebo. Conclusion: Oral administration of MAEC would have a potential to reduce gingival inflammation clinically and immunologically in the patients with gingivitis and incipient periodontitis.

Estimation of salivary matrix metalloproteinases- 12 (MMP- 12) levels among patients presenting with oral submucous fibrosis and oral squamous cell carcinoma

BackgroundOral squamous cell carcinoma is a global threat and accounts for approximately 90% of malignant oral lesions. The emergence of oral carcinoma is linked to precancerous lesions, which act as precursors of the disease. Matrix metalloproteinases appear to play a significant role in the pathogenesis of both precancerous conditions and oral malignancies due to their participation in remodeling of the extracellular matrix.MethodologyThis is an analytical study conducted at Dow University of Health Sciences, Pakistan. Unstimulated saliva samples were collected from healthy, oral submucous fibrosis and oral squamous cell carcinoma patients. The level of MMP-12 was estimated using enzyme-linked immunosorbent assay. One-way Analysis of variance was run to determine if MMP-12 levels differ between the three groups, which was preceded by post hoc Tuckey test. MMP-12 cut off values were determined using Receiver operating characteristic curve.ResultsA significant difference in salivary MMP-12 expression was observed in OSF and OSCC (p < 0.001). The expression of salivary MMP-12 was higher in OSF and OSCC patients as compared to the healthy group (p < 0.001). The mean MMP-12 expression in OSCC appeared higher than in OSF cases (p < 0.05). MMP-12 value of ge 4.05 ng/ml and ge 4.20 ng/ml is predictive of OSF and OSCC respectively, with 100% sensitivity and specificity (p < 0.001).ConclusionIncreased expression of MMP-12 appears as the healthy patient advances to OSF and OSCC. The study results also demonstrate higher MMP-12 expression in OSCC patients as compared to OSF. Therefore, the estimation of salivary MMP-12 serves as a valuable non-invasive early diagnostic tool in diagnosing oral submucous fibrosis and oral squamous cell carcinoma.

Salivary Matrix Metalloproteinase (MMP)-1 as Non-Invasive Tool for The Diagnosis of Oral Squamous Cell Carcinoma (OSCC)

OBJECTIVE: To determine the diagnostic accuracy of salivary MMP1 as non-invasive diagnostic biomarker of OSCC through conventional sandwich ELISA technique. Analytical cross-sectional study. METHODOLOGY: Individuals with clinical suspicion for OSCC (IWCS-OSCC) were included in the study after fulfilling selection criteria. Saliva samples were collected from IWCS-OSCC. To confirm OSCC, the patients were referred for biopsy. After definitive diagnosis on biopsy, patients were labeled OSCC positive or OSCC negative. The colorimetric sandwich-ELISA test was performed on saliva samples to measure the level of MMP1. Data was entered in "Statistical Package for the Social Sciences (SPSS) -16" and levels of MMP1 were correlated with the biopsy status of patient (OSCC positive or OSCC negative). RESULTS: Our sample included twice as many males as females (2.1:1) and a wide age range of 22-77years with median age of 50yrs. Of all the IWCS-OSCC 85% were OSCC +ve and 15% were OSCC-ve. Diagnostic accuracy was measured as; Area under curve (AUC) = 0.623, Sensitivity (Sn) = 50%, Specificity (Sp)= 83.3%, Positive predictive value (PPV)= 94.4%, Negative predictive value (NPV)= 22.7% CONCLUSION: MMP1 as detected by conventional sandwich-ELISA technique is not proven as an accurate diagnostic biomarker of OSCC. KEY WORDS: OSCC; MMP1; IWCS-OSCC; Sandwich-ELISA HOW TO CITE: Zaidi SJ, Riaz N, Iqbal A, Khan AA. Salivary matrix metalloproteinase (MMP)-1 as non-invasive tool for the diagnosis of oral squamous cell carcinoma (OSCC). J Pak Dent Assoc 2021;30(1):18-23.

Estimation of serum and salivary matrix metalloproteinase levels in oral squamous cell carcinoma patients: a systematic review and meta-analysis.

IntroductionMatrix metalloproteinases (MMPs) play a pivotal role in the cancer progression, invasion, and angiogenesis.AimThis meta-analysis was conducted to evaluate the difference between oral squamous cell carcinoma (OSCC) patients and healthy controls in the serum and salivary MMP levels.Material and methodsFour databases – Web of Science, PubMed, Scopus, and Cochrane Library – were searched up to March 2019. The pooled standard mean difference (SMD) and 95% confidence interval (CI) were obtained to explain the difference between the patients and controls in the salivary and serum MMP levels. Both Egger’s and Begg’s tests were considered as the significant publication bias.ResultsThirteen case-control studies were included in the meta-analysis. Among the analyses of serum MMP levels, the serum MMP7 (SMD = 0.78; 95% CI: 0.15–1.41; p = 0.02) and MMP9 (SMD = 1.18; 95% CI: 0.51–1.84; p = 0.0005) levels were significantly higher in the OSCC patients than in the controls. In addition, the analyses of salivary MMP levels showed that the MMP1 (SMD = 0.46; 95% CI: 0.22–0.70; p = 0.0001) and MMP9 (SMD = 0.66; 95% CI: 0.19–1.12; p = 0.005) levels were significantly higher in the OSCC patients than in the controls.ConclusionsThe meta-analysis showed that the serum MMP7 and MPP9 levels as well as the salivary MMP1 and MPP9 levels were significantly higher in the OSCC patients than in the controls.

Diagnostic ability of salivary matrix metalloproteinase-9 lateral flow test point-of-care test for periodontitis.

This cross-sectional study aimed to examine the diagnostic ability of salivary matrix metalloproteinase (MMP)-9 lateral flow test (LFT) point-of-care (POC) kit and develop an algorithm for diagnosis of periodontitis. Through Seoul National Dental Hospital, 137 participants (46 LFT negatives, 91 LFT positives) were recruited. For salivary diagnostics, 150μl of the unstimulated saliva was applied to LFT-POC kit. To make a diagnosis of periodontitis, stage II-IV in modified new international classification system was used. Covariates encompassing age, sex, smoking and obesity were evaluated through face-to-face interview. Enzyme-linked immunosorbent assay was used for quantification of salivary MMP-9. To develop a diagnostic algorithm, multivariable logistic regression analysis was used. Receiver operating characteristic curve was applied for evaluating diagnostic ability. Diagnostic ability of salivary MMP-9 LFT-POC test was 0.82 (sensitivity of 0.92, specificity of 0.72) in total participants. Diagnostic algorithm using POC test resulted in a response equation, that is algorithm score = -3.675+2.877*LFT+0.034*age+0.121*sex+0.372*smoking+0.192*obesity. Diagnostic ability of the algorithm was 0.88 (sensitivity of 0.92, specificity of 0.85) with cut-off score of 0.589. Salivary MMP-9 LFT-POC kit showed appropriate diagnostic ability for periodontitis and would be an efficient tool for screening of periodontitis.

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.