Subgingival bacterial colonization profiles correlate with gingival tissue gene expression.

BACKGROUND: Periodontitis is a chronic inflammatory disease caused by the microbiota of the periodontal pocket. We investigated the association between subgingival bacterial profiles and gene expression patterns in gingival tissues of patients with periodontitis. A total of 120 patients undergoing periodontal surgery contributed with a minimum of two interproximal gingival papillae (range 2-4) from a maxillary posterior region. Prior to tissue harvesting, subgingival plaque samples were collected from the mesial and distal aspects of each tissue sample. Gingival tissue RNA was extracted, reverse-transcribed, labeled, and hybridized with whole-genome microarrays (310 in total). Plaque samples were analyzed using checkerboard DNA-DNA hybridizations with respect to 11 bacterial species. Random effects linear regression models considered bacterial levels as exposure and expression profiles as outcome variables. Gene Ontology analyses summarized the expression patterns into biologically relevant categories. RESULTS: Wide inter-species variation was noted in the number of differentially expressed gingival tissue genes according to subgingival bacterial levels: Using a Bonferroni correction (p < 9.15 x 10(-7)), 9,392 probe sets were differentially associated with levels of Tannerella forsythia, 8,537 with Porphyromonas gingivalis, 6,460 with Aggregatibacter actinomycetemcomitans, 506 with Eikenella corrodens and only 8 with Actinomyces naeslundii. Cluster analysis identified commonalities and differences among tissue gene expression patterns differentially regulated according to bacterial levels. CONCLUSION: Our findings suggest that the microbial content of the periodontal pocket is a determinant of gene expression in the gingival tissues and provide new insights into the differential ability of periodontal species to elicit a local host response.

Heterogeneity of systemic inflammatory responses to periodontal therapy.

AIMS: We investigated the effect of comprehensive periodontal therapy on the levels of multiple systemic inflammatory biomarkers. MATERIAL AND METHODS: Thirty patients with severe periodontitis received comprehensive periodontal therapy within a 6-week period. Blood samples were obtained at: 1-week pre-therapy (T1), therapy initiation (T2), treatment completion (T3), and 4 weeks thereafter (T4). We assessed the plasma concentrations of 19 biomarkers using multiplex assays, and serum IgG antibodies to periodontal bacteria using checkerboard immunoblotting. At T2 and T4, dental plaque samples were analysed using checkerboard hybridizations. RESULTS: At T3, PAI-1, sE-selectin, sVCAM-1, MMP-9, myeloperoxidase, and a composite summary inflammatory score (SIS) were significantly reduced. However, only sE-selectin, sICAM, and serum amyloid P sustained a reduction at T4. Responses were highly variable: analyses of SIS slopes between baseline and T4 showed that approximately 1/3 and 1/4 of the patients experienced a marked reduction and a pronounced increase in systemic inflammation, respectively, while the remainder were seemingly unchanged. Changes in inflammatory markers correlated poorly with clinical, microbiological and serological markers of periodontitis. CONCLUSIONS: Periodontal therapy resulted in an overall reduction of systemic inflammation, but the responses were inconsistent across subjects and largely not sustainable. The determinants of this substantial heterogeneity need to be explored further.

Transcriptomes in healthy and diseased gingival tissues.

BACKGROUND: Clinical and radiographic measures are gold standards for diagnosing periodontitis but offer little information regarding the pathogenesis of the disease. We hypothesized that a comparison of gene expression signatures between healthy and diseased gingival tissues would provide novel insights in the pathobiology of periodontitis and would inform the design of future studies. METHODS: Ninety systemically healthy non-smokers with moderate to advanced periodontitis (63 with chronic periodontitis and 27 with aggressive periodontitis) each contributed at least two diseased interproximal papillae (with bleeding on probing [BOP], probing depth [PD] > or =4 mm, and attachment loss [AL] > or =3 mm) and a healthy papilla, if available (no BOP, PD < or =4 mm, and AL < or =2 mm). RNA was extracted, amplified, reverse-transcribed, labeled, and hybridized with whole genome microarrays. Differential expression was assayed in 247 individual tissue samples (183 from diseased sites and 64 from healthy sites) using a standard mixed-effects linear model approach, with patient effects considered random with a normal distribution and gingival tissue status considered a two-level fixed effect. Gene ontology analysis classified the expression patterns into biologically relevant categories. RESULTS: Transcriptome analysis revealed that 12,744 probe sets were differentially expressed after adjusting for multiple comparisons (P <9.15 x 10(7)). Of those, 5,295 were upregulated and 7,449 were downregulated in disease compared to health. Gene ontology analysis identified 61 differentially expressed groups (adjusted P <0.05), including apoptosis, antimicrobial humoral response, antigen presentation, regulation of metabolic processes, signal transduction, and angiogenesis. CONCLUSION: Gingival tissue transcriptomes provide a valuable scientific tool for further hypothesis-driven studies of the pathobiology of periodontitis.

Periodontal infections and atherosclerotic vascular disease: an update.

The role of periodontal infections as a putative risk factor for atherosclerotic vascular disease (ASVD) has been reported in the literature over the past decade. This review provides insights into biologically plausible pathways that can potentially mediate such an association, and discusses recent findings from epidemiological studies and intervention trials. Accumulating epidemiological evidence suggests that clinical, microbiological and serological markers of periodontal infection are associated with subclinical and manifest ASVD. Early evidence from intervention studies suggests that the control of periodontal infections may result in improved levels of markers of systemic inflammation and measures of endothelial dysfunction. The extent to which the control of periodontal infections results in lower incidence of ASVD events is logistically difficult to assess and has not been addressed in any study so far.

Precision of landmark positioning on digitized models from patients with cleft lip and palate.

OBJECTIVE: To quantify the precision of landmark positioning on digitized casts of patients with unilateral cleft lip and palate. PATIENTS: Forty plaster models of newborns up to 8 months of age were selected from the archive of the Department of Orthodontics of the University of Heidelberg. MATERIAL AND METHOD: The plaster-cast models were digitized with a Micromeasure 70 three-dimensional laser scanner (Micromeasure, Bischoffen, Germany). The laser scanner used in this study operates with a precision of 0.15 mm on the x- and y-axes and 0.06 mm on the z-axis. In the intraobserver study, a single observer placed anatomical landmarks in four rounds, with at least 4 weeks between each round. In the interobserver study, four different observers each placed the same landmarks once. For the two different studies, an ideal location for each landmark was calculated by averaging the landmark positions of the four rounds or observers. The distance between each of the four landmark positions and the ideal landmark was measured. RESULTS: A 95% confidence interval for the landmark positioning error was calculated. For the intraobserver investigation, this error was 0.34 to 1.30 mm, and for the interobserver investigation it was 0.7 to 2.00 mm. CONCLUSION: Because both investigations displayed comparable error intervals, it was concluded that different observers could perform landmark positioning for the same studies.