Entamoeba gingivalis Causes Oral Inflammation and Tissue Destruction.

A metagenomics analysis showed a strongly increased frequency of the protozoan Entamoeba gingivalis in inflamed periodontal pockets, where it contributed the second-most abundant rRNA after human rRNA. This observation and the close biological relationship to Entamoeba histolytica, which causes inflammation and tissue destruction in the colon of predisposed individuals, raised our concern about its putative role in the pathogenesis of periodontitis. Histochemical staining of gingival epithelium inflamed from generalized severe chronic periodontitis visualized the presence of E. gingivalis in conjunction with abundant neutrophils. We showed that on disruption of the epithelial barrier, E. gingivalis invaded gingival tissue, where it moved and fed on host cells. We validated the frequency of E. gingivalis in 158 patients with periodontitis and healthy controls by polymerase chain reaction and microscopy. In the cases, we detected the parasite in 77% of inflamed periodontal sites and 22% of healthy sites; 15% of healthy oral cavities were colonized by E. gingivalis. In primary gingival epithelial cells, we demonstrated by quantitative real-time polymerase chain reaction that infection with E. gingivalis but not with the oral bacterial pathogen Porphyromonas gingivalis strongly upregulated the inflammatory cytokine IL8 (1,900 fold, P = 2 × 10-4) and the epithelial barrier gene MUC21 (8-fold, P = 7 × 10-4). In gingival fibroblasts, we showed upregulation of the collagenase MMP13 (11-fold, P = 3 × 10-4). Direct contact of E. gingivalis to gingival epithelial cells inhibited cell proliferation. We indicated the strong virulence potential of E. gingivalis and showed that the mechanisms of tissue invasion and destruction are similar to the colonic protozoan parasite E. histolytica. In conjunction with abundant colonization of inflamed periodontal sites and the known resistance of Entamoeba species to neutrophils, antimicrobial peptides, and various antibiotics, our results raise the awareness of this protozoan as a potential and, to date, underrated microbial driver of destructive forms of periodontitis.

Smoking Modifies the Genetic Risk for Early-Onset Periodontitis.

Periodontitis has low-prevalence, highly severe disease manifestations with an early onset and rapid progression. The diagnosis is based on severe destruction of the alveolar bone in adolescents and young adults. Genetic susceptibility variants and smoking are well-established risk factors, but their interactions in modifying disease susceptibility have not been studied. We aimed to identify genetic risk variants of early-onset periodontitis that unmask their effects on tobacco smoke exposure. To this end, we analyzed 79,780,573 common variants in 741 northwest Europeans diagnosed to have >30% bone loss at >2 teeth before 35 y of age, using imputed genotypes of the OmniExpress BeadChip. Never versus ever smokers were compared in a logistic regression analysis via a case-only approach. To explore the effect of tobacco smoke on the expression of the G×S-associated genes, cultures of primary gingival fibroblasts (n = 9) were exposed to cigarette smoke extract, and transcripts were quantified by reverse transcription polymerase chain reaction. We identified 16 loci for which our analysis suggested an association with G×S increased disease risk (P < 5 × 10-5). Nine loci had previously been reported to be associated with spirometric measures of pulmonary function by an earlier G×S genome-wide association study. Genome-wide significant cis expression quantitative trait loci were reported for G×S-associated single-nucleotide polymorphisms at ST8SIA1 and SOST, indicating a causal role of these genes in tobacco-related etiopathology. Notably, SOST is a negative regulator of bone growth, and ST8SIA1 has a role in tissue remodeling. Cigarette smoke extract significantly altered the expression of 2 associated genes: SSH1 (P = 5 × 10-07), which is required for NF-κB activation and innate immune responses to bacterial invasion, and ST8SIA1 (P = 0.0048). We conclude that the genetic predisposition to early-onset periodontitis is in part triggered by smoking and that tobacco smoke directly affects the expression of genes involved in bone homeostasis, tissue repair, and immune response.

[Computer-assisted open-wedge osteotomy]. / Computerassistierte valgisierende Tibiakopfosteotomie.

AIM: The open-wedge high tibial osteotomy is an established procedure for the treatment of the unicompartimental gonarthrosis in young patients. An adequate correction of osseous malalignment is crucial for a sufficient reduction of stress in a diseased compartment. We have examined reliability and precision of an intraoperatively used computer-assisted navigation system for high tibial osteotomy. The aim of the study is to show the equivalent safety and effectiveness of high tibial osteotomies carried out with the computer-assisted navigation system. It is assumed that a good correlation between the mechanical tibio-femoral axis as measured by radiography and by the navigation system can be achieved. METHOD: 40 medial open-wedge osteotomies were performed with computer-assisted navigation on 39 patients (27 males, 12 females) between 1/2004 and 8/2006. The average age was 46.3 years (range: 26 - 64 years), the average weight was 83.2 kg (range: 54 - 118 kg). RESULTS: A good correlation between radiographic data and the data acquired with the navigation system was found for the tibio-femoral axis: preoperative data (8.0 +/- 2.5 degrees, radiographic; 7.8 +/- 2.1 degrees navigated) for varus alignment. The postoperative correlation was lower than the preoperative one (postoperative data (0.6 +/- 3.2 degrees radiographic; - 0.7 +/- 1.0 degrees navigated) for valgus alignment. In 2 patients a loss of correction occurred and had to be treated operatively. CONCLUSION: High tibial osteotomy is an established therapy procedure for unicompartmental gonarthrosis. It can be improved in its precision and reliability by computer-assisted navigation.