• Journal of Periodontal and Implant Science
• /
• v.35 no.3
• /
• pp.661-674
• /
• 2005

The purpose of this study was to quantify and compare the level of MMP-2, MMP-8 in the healthy, inflammed gingival tissue and inflammed gingival tissue associated with type 2 DM. We investigate whether expression of MMP-2, MMP-8 is increased by chronic periodontitis associated with type 2 DM. Gingival tissue samples were obtained during periodontal surgery or tooth extraction. Based on patient's systemic condition & clinical criteria of gingiva, each gingival samples were divided into three groups. Group l(n=8) is clinically healthy gingiva without bleeding and no evidence of bone resorption or periodontal pockets, obtained from 8 systemically healthy patients. Group 2(n=8) is inflammed gingiva from patients with chronic periodontitis. Group 3(n=8) is inflammed gingiva from type 2 diabetic patients with chronic periodontitis. Tissue samples were prepared and analyzed by Western blotting. The quantification of MMP-2, MMP-8 was performed using a densitometer and statistically analyzed by ANOVA. MMP-2, MMP-8 was expressed in all samples including healthy gingiva and increased in group 3 compared to group 1 and 2, and showed that significant variation was observed between group 1 & 3 in MMP-8 results. In conclusion, this study demonstrated that human gingival tissue with chronic periodontitis associated to type 2 diabetes showed slightly elevated MMP-2, MMP-8 levels compared to healthy gingiva and non-diabetic inflamed gingiva.

• Animal Bioscience
• /
• v.36 no.8
• /
• pp.1167-1179
• /
• 2023

Objective: Matrix metalloproteinases (MMPs) are a family of endoproteases produced by various tissues and cells and play important roles in angiogenesis, tissue repair, immune response, and endometrial remodeling. However, the expression and function of MMPs in the pig endometrium during the estrous cycle and pregnancy have not been fully elucidated. Thus, we determined the expression, localization, and regulation of MMP2, MMP8, MMP9, MMP12, and MMP13 in the endometrium throughout the estrous cycle and at the maternal-conceptus interface during pregnancy in pigs. Methods: Endometrial tissues during the estrous cycle and pregnancy and conceptus and chorioallantoic tissues during pregnancy were obtained and the expression of MMPs was analyzed. The effects of steroid hormones and cytokines on the expression of MMPs were determined in endometrial explant cultures. Results: Expression levels of MMP12 and MMP13 changed during the estrous cycle, while expression of MMP2, MMP9, MMP12, and MMP13 changed during pregnancy. Expression of MMP2, MMP8, and MMP13 mRNAs was cell type-specific at the maternal-conceptus interface. Gelatin zymography showed that enzymatically active MMP2 was present in endometrial tissues. In endometrial explant cultures, estradiol-17β induced the expression of MMP8 and MMP12, progesterone decreased the expression of MMP12, interleukin-1β increased the expression of MMP2, MMP8, MMP9, and MMP13, and interferon-γ increased the expression of MMP2. Conclusion: These results suggest that MMPs expressed in response to steroids and cytokines play an important role in the establishment and maintenance of pregnancy by regulating endometrial remodeling and processing bioactive molecules in pigs.

• Biomolecules & Therapeutics
• /
• v.22 no.5
• /
• pp.414-419
• /
• 2014

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that regulate cell-matrix composition and are also involved in processing various bioactive molecules such as cell-surface receptors, chemokines, and cytokines. Our group recently reported that MMP-3, -8, and -9 are upregulated during microglial activation and play a role as proinflammatory mediators (Lee et al., 2010, 2014). In particular, we demonstrated that MMP-8 has tumor necrosis factor alpha (TNF-${\alpha}$)-converting enzyme (TACE) activity by cleaving the prodomain of TNF-${\alpha}$ and that inhibition of MMP-8 inhibits TACE activity. The present study was undertaken to compare the effect of MMP-8 inhibitor (M8I) with those of inhibitors of other MMPs, such as MMP-3 (NNGH) or MMP-9 (M9I), in their regulation of TNF-${\alpha}$ activity. We found that the MMP inhibitors suppressed TNF-${\alpha}$ secretion from lipopolysaccharide (LPS)-stimulated BV2 microglial cells in an order of efficacy: M8I>NNGH>M9I. In addition, MMP inhibitors suppressed the activity of recombinant TACE protein in the same efficacy order as that of TNF-${\alpha}$ inhibition (M8I>NNGH>M9I), proving a direct correlation between TACE activity and TNF-${\alpha}$ secretion. A subsequent pro-TNF-${\alpha}$ cleavage assay revealed that both MMP-3 and MMP-9 cleave a prodomain of TNF-${\alpha}$, suggesting that MMP-3 and MMP-9 also have TACE activity. However, the number and position of cleavage sites varied between MMP-3, -8, and -9. Collectively, the concurrent inhibition of MMP and TACE by NNGH, M8I, or M9I may contribute to their strong anti-inflammatory and neuroprotective effects.

• Journal of dental hygiene science
• /
• v.14 no.4
• /
• pp.525-536
• /
• 2014

Although tobacco use has been known as one of the biggest risk factors on periodontal health, little is known about the effect of smoking cessation on it. The aim of this study was to investigate the change of concentration of matrix metalloproteinase (MMP)-8, MMP-9 and interleukin (IL)-$1{\beta}$ in gingival crevicular fluid (GCF) of 11 quit-smokers for 1 year after smoking cessation. Eleven male subjects to maintain quit-smoking for 1 year participated the oral examination, GCF and saliva collection without periodontal treatments at baseline, after 2 weeks, 2 months, 4 months, 6 months and 1 year. To confirm quit-smoking, nicotine and cotinine concentrations in saliva were measured by high performance liquid chromatography. MMP-8, MMP-9 and IL-$1{\beta}$ concentrations in GCF of upper anterior teeth area were measured by enzyme-linked immunosorbent assay. Change of MMP-8 in GCF during smoking cessation showed fluctuation with decrease (5 subjects) or increase (2 subjects) or maintenance tendency (4 subjects). Changes of MMP-9 were decrease (6 subjects), or increase (2 subjects), or maintenance (3 subjects). Change of IL-$1{\beta}$ also showed fluctuation with decrease (5 subjects) or increase (3 subjects) or maintenance tendency (3 subjects). The subjects with increase tendency had the relatively smaller amount concentration of MMP-8 and MMP-9 at the baseline. It was unclear smoking cessation without periodontal treatment could affect MMP-8, MMP-9, and IL-$1{\beta}$ in GCF. Fluctuation of periodontal biomarkers during smoking cessation might result from feedback interaction between environmental factors and periodontal cells.

• Restorative Dentistry and Endodontics
• /
• v.30 no.2
• /
• pp.138-144
• /
• 2005

This in vitro study monitored MMP-8 production on PMN by stimulated with the following three groups; Sonicated extracts of E. faecalis (SEF), SEF treated with $Ca(OH)_2$ (12.5mg/ml) for 7 days, and lipopolysac-charides(LPS) of E. coli. The level of MMP-8 in each group was immediately measured by ELISA. The data were analyzed with Kruskal-Wallis test and Mann-Whitney U test. In the SEF group, the level of production of MMP-8 was higher than the negative control group in low concentration ($0.05{\mu}g/ml$) of SEF (p < 0.05). but it decreased with an increase in the concentration of SEF (p < 0.05). In the case of SEF treated with $Ca(OH)_2$, all of the MMP levels were higher than negative control group (p < 0.05), but no statistical difference was found among the different SEF concentrations (p > 0.05). All of the levels in E. coli LPS were incresed with increasing concentrations (p < 0.05). According to this study we could summarized as follows: 1. MMP-8 was expressed at low level in untreated PMN group the levels of MMP-8 were upregulated in PMN stimulated by E. coli LPS groups. 2. In the SEF groups, the level of production of MMP-8 decreased with an increase in concentration of SEF (p < 0.05). So E. faecalis may have suppressive effect on the production of MMP-8 by PMN. 3. In the case of SEF treated with $Ca(OH)_2$, all of the MMP levels at different SEF concentrations were higher than untreated PMN group (p < 0.05), but no statistical difference was found among the different SEF concentrations (p > 0.05).

• Journal of dental hygiene science
• /
• v.12 no.1
• /
• pp.71-77
• /
• 2012

Sex Hormones exert significant influence in body physiology throughout life. Some reports suggested increased sex hormone levels correlate with an increased prevalence of gingivitis. The objectives of this pilot study are to(1) address the link between menstrual cycle and MMP-9, MMP-8, IL-$1{\beta}$ of gingival crevicular fluid during 4 weeks and (2) discuss the major biomarker of periodontal status. 7 female and 3 male volunteer who didn't have smoking habit, medical and dental disease after informed consent, were seen twice a week for 4 weeks. GCF samples were collected and GCF levels of MMP-9, MMP-8, IL-$1{\beta}$ were measured by enzyme-linked immunosorbent assay. The GCF levels of MMP-9, MMP-8, IL-$1{\beta}$ had fluctuation according to menstrual cycle, but the changes of those were not significant by Friedman matched samples test. There is no difference between female and male subjects by Mann-Whitney U test. The correlation of MMP-8, MMP-9 and IL-$1{\beta}$ showed strong by Spearman correlation(0.644-0.945). This study confirms menstrual cycle doesn't influence the periodontium of healthy female subjects.

• Journal of Periodontal and Implant Science
• /
• v.48 no.4
• /
• pp.251-260
• /
• 2018

Purpose: The aim of this retrospective cross-sectional study was to evaluate whether salivary findings of active matrix-metalloproteinase 8 (aMMP-8) chairside (point of care; POC) tests were associated with periodontal risk assessment parameters in patients receiving supportive periodontal therapy (SPT). Methods: A total of 125 patients receiving regular SPT were included, and their records were examined. The following inclusion criteria were used: a diagnosis of chronic periodontitis, at least 1 non-surgical periodontal treatment (scaling and root planning) with following regular SPT (minimum once a year), at least 6 remaining teeth, and clinical and aMMP-8 findings that were obtained at the same appointment. In addition to anamnestic factors (e.g., smoking and diabetes), oral hygiene indices (modified sulcus bleeding index [mSBI] and approximal plaque index), periodontal probing depth simultaneously with bleeding on probing, and dental findings (number of decayed, missing, and filled teeth) were recorded. Salivary aMMP-8 levels were tested using a commercial POC test system (Periomarker, Hager & Werken, Duisburg, Germany). Statistical analysis was performed using the t-test, Mann-Whitney U test, Fisher's exact test, and ${\chi}^2$ test, as appropriate (P<0.05). Results: Only the mSBI was significantly associated with positive salivary aMMP-8 findings (aMMP-8 positive: $27.8%{\pm}20.9%$ vs. aMMP-8 negative: $18.0%{\pm}14.5%$; P=0.017). No significant associations were found between aMMP-8 and smoking, diabetes, periodontal parameters, or parameters related to the maintenance interval (P>0.05). Conclusions: Salivary aMMP-8 chairside findings were not associated with common parameters used for periodontal risk assessment in patients receiving SPT. The diagnostic benefit of POC salivary aMMP-8 testing in risk assessment and maintenance interval adjustment during SPT remains unclear.

• Biomolecules & Therapeutics
• /
• v.29 no.5
• /
• pp.483-491
• /
• 2021

Parkinson's disease (PD) is a neurodegenerative disorder that involves the loss of dopaminergic neurons in the substantia nigra (SN). Matrix metalloproteinases-8 (MMP-8), neutrophil collagenase, is a functional player in the progressive pathology of various inflammatory disorders. In this study, we administered an MMP-8 inhibitor (MMP-8i) in Leucine-rich repeat kinase 2 (LRRK2) G2019S transgenic mice, to determine the effects of MMP-8i on PD pathology. We observed a significant increase of ionized calcium-binding adapter molecule 1 (Iba1)-positive activated microglia in the striatum of LRRK2 G2019S mice compared to normal control mice, indicating enhanced neuro-inflammatory responses. The increased number of Iba1-positive activated microglia in LRRK2 G2019S PD mice was down-regulated by systemic administration of MMP-8i. Interestingly, this LRRK2 G2019S PD mice showed significantly reduced size of cell body area of tyrosine hydroxylase (TH) positive neurons in SN region and MMP-8i significantly recovered cellular atrophy shown in PD model indicating distinct neuro-protective effects of MMP-8i. Furthermore, MMP-8i administration markedly improved behavioral abnormalities of motor balancing coordination in rota-rod test in LRRK2 G2019S mice. These data suggest that MMP-8i attenuates the pathological symptoms of PD through anti-inflammatory processes.

• Restorative Dentistry and Endodontics
• /
• v.36 no.3
• /
• pp.196-202
• /
• 2011

Objectives: The aim of this study was to investigate levels of matrix metalloproteinase-8 (MMP-8) and substance P (SP) in root canal exudates during root canal treatment (RCT) of nonvital, painful teeth. Materials and Methods: Patients scheduled for nonsurgical RCT were prospectively selected; the study was performed after obtaining informed consent from the patients and was approved by the Institutional Review Board for Clinical Research of Gangnam Severance Hospital, Yonsei University (3-2008-0118). Canal exudates samples were collected using sterilized paper points from teeth scheduled for RCT across three different time periods. MMP-8 and SP levels were measured using enzyme-linked immunosorbent assay (ELISA). Data were analyzed using a mixed model analysis and the Pearson correlation analysis (p < 0.05). Results: MMP-8 and SP levels in GCF were decreased during RCT (p < 0.0001), and they showed a weak positive correlation to each other (p < 0.05). Patients' subjective pain levels and the response from percussion test were significantly related to SP level. Conclusions: This study demonstrated that periradicular inflammation endodontic origin can elevate SP and MMP-8 levels in root canal exudates. Interestingly, SP level of canal exudates showed a possibility of being used as an indicator of pain due to periapical pathosis.

• Clinical and Experimental Pediatrics
• /
• v.57 no.12
• /
• pp.526-532
• /
• 2014

Purpose: Matrix metalloproteinases (MMPs) have been implicated in atherosclerosis, and therefore, are considered risk factors for metabolic dysfunction in adults. However, there is little data on circulating levels of MMPs and tissue inhibitors of MMPs (TIMPs) with regard to obesity-related biomarkers in the general adolescent population. In the present study, we determined the associations of MMP-8, MMP-9, and TIMP-1 levels and MMP-8/TIMP-1 and MMP-9/TIMP-1 ratios with obesity-related biomarkers in apparently healthy adolescent boys. Methods: We measured MMP and TIMP concentrations in plasma samples using the enzyme-linked immunosorbent assay and analyzed their associations with obesity-related biomarkers, such as liver enzymes and lipid profiles, in a sample of 91 Korean boys aged 13-14 years who participated in a general health check-up. Results: The mean age of the boys was $13.8{\pm}0.3years$; 72 boys were normal weight and 19 were overweight/obese. The Pearson correlation coefficients revealed a significant correlation between MMP-8 and aspartate aminotransferase (r=0.217, P=0.039) and alanine aminotransferase (r=0.250, P=0.017) and between TIMP-1 and aspartate aminotransferase (r=0.267, P=0.011). In a multivariate linear regression analysis, serum alanine aminotransferase was positively associated with the MMP-8 level. There were no significant differences in the MMP-8, MMP-9, and TIMP-1 levels or MMP-8/TIMP-1 and MMP-9/TIMP-1 ratios between control and overweight/obese subjects. Conclusion: We found a significant association between the MMP-8 level and alanine aminotransferase in the apparently healthy adolescent boys. These findings indicate that there may be a pathophysiological mechanism underlying the relationship between MMP-8 and liver enzymes in young adolescents.