Nicole Pischon

Obesity, Inflammation, and Periodontal Disease

The prevalence of obesity has increased substantially over the past decades in most industrialized countries. Obesity is a systemic disease that predisposes to a variety of co-morbidities and complications that affect overall health. Cross-sectional studies suggest that obesity is also associated with oral diseases, particularly periodontal disease, and prospective studies suggest that periodontitis may be related to cardiovascular disease. The possible causal relationship between obesity and periodontitis and potential underlying biological mechanisms remain to be established; however, the adipose tissue actively secretes a variety of cytokines and hormones that are involved in inflammatory processes, pointing toward similar pathways involved in the pathophysiology of obesity, periodontitis, and related inflammatory diseases. We provide an overview of the definition and assessment of obesity and of related chronic diseases and complications that may be important in the periodontist’s office. Studies that have examined the association between obesity and periodontitis are reviewed, and adipose-tissue-derived hormones and cytokines that are involved in inflammatory processes and their relationship to periodontitis are discussed. Our aim is to raise the periodontist’s awareness when treating obese individuals.

The association between rheumatoid arthritis and periodontal disease

Chronic, plaque-associated inflammation of the gingiva and the periodontium are among the most common oral diseases. Periodontitis (PD) is characterized by the inflammatory destruction of the periodontal attachment and alveolar bone, and its clinical appearance can be influenced by congenital as well as acquired factors. The existence of a rheumatic or other inflammatory systemic disease may promote PD in both its emergence and progress. However, there is evidence that PD maintains systemic diseases. Nevertheless, many mechanisms in the pathogenesis have not yet been examined sufficiently, so that a final explanatory model is still under discussion, and we hereby present arguments in favor of this. In this review, we also discuss in detail the fact that oral bacterial infections and inflammation seem to be linked directly to the etiopathogenesis of rheumatoid arthritis (RA). There are findings that support the hypothesis that oral infections play a role in RA pathogenesis. Of special importance are the impact of periodontal pathogens, such as Porphyromonasgingivalis on citrullination, and the association of PD in RA patients with seropositivity toward rheumatoid factor and the anti-cyclic citrullinated peptide antibody.

Porphyromonas gingivalis Strain-Dependent Activation of Human Endothelial Cells

ABSTRACT Porphyromonas gingivalis is an important bacterium involved in periodontal diseases. Colonization by periodontopathogens has been associated with severe local inflammatory reactions in the connective tissue. In this study we characterized P. gingivalis-mediated infection and activation of human umbilical vein endothelial cells by using two strains of different virulence capacities, strains ATCC 53977 and DSMZ 20709. Both strains were able to adhere to and infect endothelial cells with an infection rate of 0.48% for ATCC 53977 and 0.007% for DSMZ 20709. The triggering of two signal transduction pathways in P. gingivalis-infected endothelial cells was demonstrated for both strains, with a rapid increase of p38 mitogen-activated protein kinase phosphorylation and a more delayed degradation of IκBα, followed by nuclear translocation of NF-κB. In addition, both strains induced enhanced expression of endothelial adhesion molecules E-selectin and intracellular adhesion molecule 1 (ICAM-1). Target cell activation was independent of bacterial fimbriae expression since the fimA knockout strain A7436 ΔfimA induced the same level of ICAM-1 as the corresponding wild type (A7436-WT). Thus, two P. gingivalis strains, ATCC 53799 and DSMZ 20709, infect endothelial cells and trigger signaling cascades leading to endothelial activation, which in turn may result in or promote severe local and systemic inflammation.

Effects of Porphyromonas gingivalis on cell cycle progression and apoptosis of primary human chondrocytes

Background: It has been suggested that bacterial infections have a role in the pathogenesis of rheumatoid arthritis (RA). P gingivalis, a Gram-negative, anaerobic rod, is one of the major pathogens associated with periodontal disease. Objective: To examine P gingivalis infection and its effects on cell cycle progression and apoptosis of human articular chondrocytes. Methods: Primary human chondrocytes cultured in monolayers were challenged with P gingivalis. Infection and invasion of P gingivalis into chondrocytes was analysed by scanning electron microscopy, double immunofluorescence and by antibiotic protection and invasion assay. Cell cycle progression of infected chondrocytes was evaluated by flow cytometry. Also, cell apoptosis was visualised by terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) of DNA strand breaks and by western blot analysis. Results: Data showed that P gingivalis could adhere and infect primary human chondrocytes. After chondrocyte infection, intracellular localisation of P gingivalis was noted. Flow cytometry analyses demonstrated affected cell cycle progression, with an increase of the G1 phase and a significant decrease of the G2 phase after infection. In addition, increased apoptosis of P gingivalis-infected chondrocytes was visualised by TUNEL assay and by upregulation of caspase-3 protein expression. Conclusion: These data demonstrate that P gingivalis infects primary human chondrocytes and affects cellular responses, which might contribute to the tissue damage seen in the pathogenesis of rheumatoid arthritis.

Periodontal disease in patients with ankylosing spondylitis

Objective: Ankylosing spondylitis (AS) and periodontal disease (PD) are characterised by dysregulation of the host inflammatory response, resulting in soft and hard connective tissue destruction. AS has been related to other inflammatory diseases, however, there is a paucity of data on whether AS is associated with inflammatory PD. Methods: The association between AS and PD was examined in 48 patients with AS and 48 healthy controls, matched for age and gender. AS was diagnosed according to the modified New York criteria. Periodontal examination included probing pocket depth (PPD), clinical attachment loss (CAL), plaque index (PI) and bleeding on probing (BOP). Potential risk factors of PD such as smoking, low education, alcohol consumption, body mass index (BMI), as well as chronic diseases associated with PD and AS were assessed through questionnaires. Results: In stepwise logistic regression, including AS status, age, gender, education, smoking, alcohol consumption and BMI, only AS status, age and education remained significant predictors of PD. Patients with AS had significant 6.81-fold increased odds (95% CI 1.96 to 23.67) of PD (defined as mean attachment loss >3 mm) compared to controls. The strength of the association was attenuated but remained statistically significant after further adjustment for plaque accumulation (odds ratio (OR) 5.48, 95% CI 1.37 to 22.00). Conclusions: The present study shows that patients with AS have a significantly higher risk of PD, strongly suggesting the need for close collaboration between rheumatologists, periodontists and dental hygienists when treating patients with AS.

Induced Apoptosis of Chondrocytes by Porphyromonas gingivalis as a Possible Pathway for Cartilage Loss in Rheumatoid Arthritis

The role of bacterial infections in the pathogenesis of rheumatoid arthritis (RA) has gained increasing interest. Patients with RA often exhibit periodontal disease, which is associated with pathogens like Porphyromonas gingivalis. The present study examines the direct effects of P. gingivalis on apoptosis of human chondrocytes (a feature of inflammatory joint diseases) as one can assume an interrelation of pathogenesis of RA and P. gingivalis infections. Primary chondrocytes were infected with P. gingivalis. Early apoptotic and dead cell analysis was performed using Annexin-V, 7AAD, and propidium iodide and examined by flow cytometry and fluorescence microscopy. Caspase activation and DNA fragmentation were determined by western blot analysis and TUNEL reaction. Flow cytometry and fluorescence microscopy demonstrated an increase of Annexin-V-positive early apoptotic chondrocytes after infection. Western blot showed upregulation of activated caspase-3 expression, and TUNEL reaction revealed considerable DNA fragmentation following infection. The data show that P. gingivalis promotes early and later stages of apoptosis of primary human chondrocytes, which might contribute to the joint damage seen in the pathogenesis of RA.

Smoking, Smoking Cessation, and Risk of Tooth Loss The EPIC-Potsdam Study

The aim of this study was to investigate the association between cigarette smoking and smoking cessation and the prevalence and incidence of tooth loss in a large cohort study in Germany. We analyzed data of 23,376 participants of the European Prospective Investigation into Cancer and Nutrition (EPIC)–Potsdam study recruited between 1994 and 1998 from the general population in Potsdam and other parts of Brandenburg, Germany, who had complete data on cigarette smoking, tooth loss, and covariates. Negative binomial regression and tooth-specific logistic regression models were fit to evaluate the association between smoking and the baseline prevalence and incidence of tooth loss during follow-up, respectively. Cigarette smoking was associated with higher prevalence of tooth loss at baseline as well as higher incidence of tooth loss during follow-up. The association between smoking and the incidence of tooth loss was stronger in men than women and stronger in younger versus older individuals. Heavy smoking (≥15 cigarettes/d) was associated with >3 times higher risk of tooth loss in men (odds ratio, 3.6; 95% confidence interval, 3.0, 4.4) and more than twice the risk of tooth loss in women (odds ratio, 2.5; 95% confidence interval, 2.1, 2.9) younger than 50 y when compared with never smokers. Smoking cessation was consistently associated with a reduction in tooth loss risk, with the risk of tooth loss approaching that of never smokers after approximately 10 to 20 y of cessation.

Association between Number of Teeth and Chronic Systemic Diseases: A Cohort Study Followed for 13 Years

Background There is growing evidence of an association between oral health, specifically dental status, and chronic systemic diseases. However, varying measures of dental status across different populations and low study sample has made comparison of studies and conclusion of findings unclear. Our aim is to examine whether the number of teeth as a measure of dental status is associated with incident chronic diseases in a cohort setting. Methods We conducted a cohort study among 24,313 middle-aged Germans followed up for 13 years. Data on number of teeth as a measure of dental status were obtained through self-reports. Outcomes were clinically–verified incident non–fatal myocardial infarction, stroke, type 2 diabetes mellitus, and cancer. Hazard ratio (HR) and 95% confidence intervals (CI) were obtained from Cox regression models. Results Increasing number of teeth is inversely related to risk of myocardial infarction (HR: 0.97; 95% CI: 0.96, 0.99). The full multivariate model of teeth groups showed a strong linear trend for myocardial infarction, a less strong trend for stroke, and no relation with type 2 diabetes mellitus and cancer in a competing risk model. Participants with 18–23 teeth and those without teeth were at 76% (95%CI: 1.04, 3) and 2.93 times (95%CI: 1.61, 5.18) higher risk of myocardial infarction compared to those with nearly all teeth (28–32 teeth). Conclusions Number of teeth is specifically associated with myocardial infarction and not with other chronic disease indicating that dental status further strengthens the link between oral health and cardiovascular diseases.

The impact of Porphyromonas gingivalis lipids on apoptosis of primary human chondrocytes.

The role of oral bacterial infections including periodontal disease in the pathogenesis of rheumatoid arthritis (RA) has gained increasing interest. Among the major periodontal pathogens, Porphyromonas gingivalis has been mostly associated with RA pathogenesis. The aim of this study was to analyze the effect of P. gingivalis total lipid (TL) fraction and dihydroceramides, as potent virulence factors, on human primary chondrocytes. Primary chondrocyte cultures were incubated with P. gingivalis phosphoglycerol dihydroceramide (PG DHC) lipids, the TL fraction or phosphoethanolamine dihydroceramide. Cell morphology changes were determined by phase contrast light microscopy. Early and late apoptosis cell analysis was performed by Annexin-V, active caspases, and 7-Aminoactinomycin D staining, and examined by flow cytometry, and cell necrosis was evaluated by lactate dehydrogenase release. Procaspase-3 activation was determined by Western blot analysis. Microscopic analysis showed altered cell morphology and cell shrinkage following incubation with P. gingivalis TLs and PG DHC lipids. Flow cytometry demonstrated an increase of Annexin-V positive and active caspases positive chondrocytes after incubation with TL and PG DHC fractions but not after phosphoethanolamine dihydroceramide (control lipid) treatment or in untreated control cells. Furthermore, Western blot analysis showed an early cleavage of procaspase-3 after 1 hr. Significant lactate dehydrogenase release following incubation with P. gingivalis lipids was demonstrated. The present data demonstrate that P. gingivalis lipids promote apoptosis in primary human chondrocytes, and thereby may contribute to the joint damage seen in the pathogenesis of RA.

Nanocoating with plant-derived pectins activates osteoblast response in vitro

A new strategy to improve osseointegration of implants is to stimulate adhesion of bone cells, bone matrix formation, and mineralization at the implant surface by modifying surface coating on the nanoscale level. Plant-derived pectins have been proposed as potential candidates for surface nanocoating of orthopedic and dental titanium implants due to 1) their osteogenic stimulation of osteoblasts to mineralize and 2) their ability to control pectin structural changes. The aim of this study was to evaluate in vitro the impact of the nanoscale plant-derived pectin Rhamnogalacturonan-I (RG-I) from potato on the osteogenic response of murine osteoblasts. RG-I from potato pulps was isolated, structurally modified, or left unmodified. Tissue culture plates were either coated with modified RG-I or unmodified RG-I or – as a control – left uncoated. The effect of nanocoating on mice osteoblast-like cells MC3T3-E1 and primary murine osteoblast with regard to proliferation, osteogenic response in terms of mineralization, and gene expression of Runt-related transcription factor 2 (Runx2), alkaline phosphate (Alpl), osteocalcin (Bglap), α-1 type I collagen (Col1a1), and receptor activator of NF-κB ligand (Rankl) were analyzed after 3, 7, 14, and 21 days, respectively. Nanocoating with pectin RG-Is increased proliferation and mineralization of MC3T3-E1 and primary osteoblast as compared to osteoblasts cultured without nanocoating. Moreover, osteogenic transcriptional response of osteoblasts was induced by nanocoating in terms of gene induction of Runx2, Alpl, Bglap, and Col1a1 in a time-dependent manner – of note – to the highest extent under the PA-coating condition. In contrast, Rankl expression was initially reduced by nanocoating in MC3T3-E1 or remained unaltered in primary osteoblast as compared to the uncoated controls. Our results showed that nanocoating of implants with modified RG-I beneficially 1) supports osteogenesis, 2) has the capacity to improve osseointegration of implants, and is therefore 3) a potential candidate for nanocoating of bone implants.