Association between bleeding periodontal pockets and eczemas: Results of the Northern Finland Birth Cohort 1966.

AIM: To investigate whether the periodontal condition as measured by bleeding periodontal pockets is associated with atopic dermatitis, seborrheic dermatitis, and eczema nummulare. MATERIALS AND METHODS: The study population (n = 1871) was obtained from the 46-year follow-up study of the Northern Finland Birth Cohort 1966 study (NFBC1966). The periodontal condition was measured by the number of sites with bleeding periodontal pockets that were ≥4 mm deep. The whole skin of the participants was clinically examined, and diagnoses of skin diseases were made according to the International Classification of Diseases. Prevalence rate ratios (PRR) and 95% confidence intervals (95% CIs) were estimated using Poisson regression models with robust error variance. RESULTS: In this cohort, comprising 46-year-old participants of NFBC1966, the presence of 1-3 and ≥4 bleeding-deepened periodontal pockets (≥4 mm deep) were associated with seborrheic dermatitis (PRR 1.9, 95% CI: 1.3-2.8 and PRR 2.2, 95% CI: 1.4-3.3, respectively) and with eczema nummulare (PRR 1.7, 95% CI: 0.9-3.1 and PRR 1.7, 95% CI: 0.9-3.3, respectively). For non-smokers, the corresponding estimates were 1.7 for seborrheic dermatitis (95% CI: 1.1-2.6) and 1.8 (95% CI: 1.1-3.1) and 1.4 for eczema nummulare (95% CI: 0.7-2.9) and 1.2 (95% CI: 0.5-2.9), respectively. No association was found between bleeding-deepened periodontal pockets and atopic dermatitis. Further adjustments for C-reactive protein, diabetes, and inflammatory diseases did not essentially change the risk estimates among either the total population or the non-smokers. CONCLUSION: Bleeding periodontal pockets appeared to be associated with the presence of seborrheic dermatitis and eczema nummulare.

Prevalence of oral mucosal normal variations and lesions in a middle-aged population: a Northern Finland Birth Cohort 1966 study.

BACKGROUND: In this cross-sectional study we investigated the oral mucosal changes in a middle-aged Finnish population. We analyzed the prevalence of potentially malignant disorders and the influence of smoking, snuff and alcohol use on the mucosal changes. METHODS: Of the 12,068 members of the NFBC 1966, a total of 1961 participants (16.2%) constituted the study population. Mucosal changes were diagnosed and photographed by seven general dentists, and two specialists re-analyzed all the diagnoses based on the documentation Cross-tabulation with Chi-square tests and logistic regression analysis were used to analyze the data. RESULTS: Of the participants, 10.5% had some mucosal changes, of which 81.8% were diagnosed as oral mucosal lesions (OML) and 18.2% as normal variations. Of the normal variations, the most common were Fordyce granules (1.2%), fissured tongue (1.1%) and geographic tongue (0.9%). The most common OMLs were white lesions (6.5%), of which oral lichen planus (OLP) and lichenoid reactions (OLR), grouped as oral lichenoid diseases, were present in 3.5%, males more often (3.8% vs. 3.1%). OLP was found in 1.5% of all participants, females more often (1.8% vs. 1.2%), while OLR was more common in males (2.7% vs. 1.3%). Leukoplakia was identified in 0.5% of the population; twice more often in males (0.6% vs. 0.3%). Erythroplakia was not found. Current smokers had higher risk for oral mucosal changes than former or non-smokers (OR 3.0, 95% CI 2.11-4.28), and snuff, used occasionally or regularly, also raised the risk (OR 2.6, 95% CI 1.48-4.70). CONCLUSIONS: In the middle-aged northern Finland population, 4% of OMLs were potentially malignant disorders, including OLR (2%), OLP (1.5%) and leukoplakia (0.5%). In particular, smoking and snuff use increased the risk for having any oral mucosa changes.

Trypsin-2 enhances carcinoma invasion by processing tight junctions and activating ProMT1-MMP.

Enhanced proteolysis and altered tight junction (TJ) proteins associate with carcinoma invasion. We hypothesized that trypsin-2, a tumor-associated serine proteinase, induces tongue carcinoma invasion by activating pro-membrane type-1 matrix metalloproteinase (MT1-MMP) and disturbing the TJs. The effects of invasion were analyzed using trypsin-2 over-expressing human tongue squamous cell carcinoma cells (Try2-HSC-3) in vitro and in vivo. The invasion of Try2-HSC-3 cells was increased in mouse xenografts and human organotypic model. Trypsin-2 activated proMT1-MMP, as well as altered the expression of TJ protein claudin-7. In conclusion, trypsin-2 over-expression enhanced tongue carcinoma cell invasion by various genetic and proteolytic mechanisms.

Matrix metalloproteinase-8 concentration in shallow crevices associated with the extent of periodontal disease.

OBJECTIVE: The aim of this study was to analyse the association between matrix metalloproteinase-8 (MMP-8) concentration in shallow, mostly non-bleeding gingival crevices, and the extent of periodontal disease. MATERIAL AND METHODS: Plaque, bleeding on probing (BOP), probing pocket depth (PPD) and attachment level (AL) were assessed clinically in 48 patients with chronic periodontitis. MMP-8 concentrations in gingival crevicular fluid (GCF) from four shallow (PPDor=4 mm (p=0.028) and AL>or=6 mm (p<0.001). CONCLUSION: The above association between MMP-8 concentration in shallow crevices and attachment loss provides a new aspect to future studies of MMP-8 as a prognostic marker for periodontal disease.

Intracellular co-localization of trypsin-2 and matrix metalloprotease-9: possible proteolytic cascade of trypsin-2, MMP-9 and enterokinase in carcinoma.

Tumor-associated trypsin-2 and matrix metalloprotease-9 (MMP-9) are associated with cancer, particularly with invasive squamous cell carcinomas. They require activation for catalytical competence via proteolytic cascades. One cascade is formed by enterokinase, trypsin-2 and MMP-9; enterokinase activates trypsinogen-2 to trypsin-2, which is an efficient proMMP-9 activator. We describe here that oral squamous cell carcinomas express all members of this cascade: MMP-9, trypsin-2 and enterokinase. The expression of enterokinase in a carcinoma cell line not derived from the duodenum was shown here for the first time. Enterokinase directly cleaved proMMP-9 at the Lys65-Ser66 site, but failed to activate it in vitro. We demonstrated by confocal microscopy that MMP-9 and trypsin-2 co-localized in intracellular vesicles of the carcinoma cells. This co-localization of trypsin-2 and MMP-9 resulted in intracellular proMMP-9 processing that represented fully or partially activated MMP-9. However, although both proteases were present also in various bone tumor tissues, MMP-9 and trypsin-2 never co-localized at the cellular level in these tissues. This suggests that the intracellular vesicular co-localization, storage and possible activation of these proteases may be a unique feature for aggressive epithelial tumors, such as squamous cell carcinomas, but not for tumors of mesenchymal origin.

Collagen XVIII modulation is altered during progression of oral dysplasia and carcinoma.

BACKGROUND: Collagen XVIII is a ubiquitous basement membrane (BM) component and a precursor of endostatin. METHODS: Using immunohistochemistry and in situ hybridization, we studied the expression and localization of collagen XVIII in different stages of normal oral wound healing, epithelial dysplasia and squamous cell carcinoma (SCC). RESULTS: In mild epithelial dysplasias collagen XVIII appeared as a continuous signal in the BM, whereas in severe epithelial dysplasias and in the invasive areas of oral SCCs collagen XVIII was absent. In situ hybridization showed that collagen XVIII mRNA expression did not decrease in severe dysplasia or oral carcinoma samples when compared with the mild dysplasias. CONCLUSIONS: The results indicate that the absence of collagen XVIII protein in severe oral dysplasias is related to the processing of the protein rather than to changes in mRNA expression.

Trypsins and their role in carcinoma growth.

There are more than 100 distinct types of cancer, and subtypes can be found within specific organs. Cancer progression is a complex multi-step process. These steps reflect alterations that drive the progressive transformation of normal cells into highly malignant ones. One critical step in tumor growth and invasion is the proteolytic processing of the extracellular matrix environment. The degradation of the extracellular matrix not only enables cell migration, invasion, and metastasis formation, but also affects cell behavior in multiple ways; on one hand by cleaving extracellular matrix bound growth factors and on the other hand by inhibiting angiogenesis into the tumor by liberating cryptic endogenous inhibitors of angiogenesis. Serine proteases and matrix metalloproteases are families of proteolytic enzymes involved in physiological and pathological extracellular matrix and basement membrane processing. In this review, we will focus on the role and activation of trypsinogens, a family of serine proteases, in cancer progression.