Periodontitis is a chronic inflammatory disease caused by gram-negative anaerobic bacteria. Monocytes and macrophages stimulated by periodontopathic bacteria induce inflammatory mediators that cause tooth-supporting structure destruction and alveolar bone resorption. In this study, using a DNA microarray, we identified the enhanced gene expression of thrombospondin-1 (TSP-1) in human monocytic cells stimulated by Porphyromonas gingivalis lipopolysaccharide (LPS). TSP-1 is a multifunctional extracellular matrix protein that is upregulated during the inflammatory process. Recent studies have suggested that TSP-1 is associated with rheumatoid arthritis, diabetes mellitus, and osteoclastogenesis. TSP-1 is secreted from neutrophils, monocytes, and macrophages, which mediate immune responses at inflammatory regions. However, TSP-1 expression in periodontitis and the mechanisms underlying TSP-1 expression in human monocytic cells remain unknown. Here using real-time RT-PCR, we demonstrated that TSP-1 mRNA expression level was significantly upregulated in inflamed periodontitis gingival tissues and in P. gingivalis LPS-stimulated human monocytic cell line THP-1 cells. TSP-1 was expressed via Toll-like receptor (TLR) 2 and TLR4 pathways. In P. gingivalis LPS stimulation, TSP-1 expression was dependent upon TLR2 through the activation of NF-κB signaling. Furthermore, IL-17F synergistically enhanced P. gingivalis LPS-induced TSP-1 production. These results suggest that modulation of TSP-1 expression by P. gingivalis plays an important role in the progression and chronicity of periodontitis. It may also contribute a new target molecule for periodontal therapy.

This large-scale study cross-sectionally examined the periodontal status and prevalence of "red complex" bacteria (Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia) in Japanese adults. A total of 977 participants were enrolled in the study. Probing depth (PD), bleeding on probing (BOP), and bone crest level (BCL) were recorded, and the presence of red complex bacteria in the saliva was examined using polymerase chain reaction. The mean BCL value and the percentage of sites with a PD ≥4 mm or the presence of BOP were significantly higher in older participants. The detection rates of P. gingivalis, T. denticola, and T. forsythia were 46.3%, 76.4%, and 61.1%, respectively. The P. gingivalis detection rate significantly increased with age, while those of T. denticola and T. forsythia were comparably high for all age groups. A close correlation between P. gingivalis and the percentage of sites with PD ≥4 mm was indicated by nonlinear canonical correlation analysis. Current smokers exhibited a more advanced disease condition and a significantly higher P. gingivalis detection rate than non-smokers. In conclusion, periodontal condition worsens with age, and P. gingivalis appears to be the red complex bacterium most closely associated with periodontitis.

Aggressive periodontitis (AgP) is characterized by rapid alveolar bone destruction and tooth loss early in life, and its etiology remains unclear. To explore the genetic risk factors of AgP, we performed genome-wide single-nucleotide polymorphism genotyping for identity-by-descent mapping and identified 32 distinct candidate loci, followed by whole exome sequencing with 2 pedigrees of AgP consisting of 3 cases and 1 control in 1 family and 2 sibling cases in the other. After variant filtering procedures and validation by targeted Sanger sequencing, we identified 2 missense mutations at 16q12 in NOD2 (p.Ala110Thr and p.Arg311Trp), which encodes nucleotide-binding oligomerization domain protein 2. We further examined 94 genetically unrelated AgP patients by targeted sequencing of NOD2 and found that 2 patients among them also carried the p.Arg311Trp variant. Furthermore, we found 3 additional missense mutations in this gene (p.His370Tyr, p.Arg459Cys, and p.Ala868Thr). These mutations either had not been previously observed or are extremely rare (frequency <0.001) in Asian populations. NOD2 plays a crucial role in innate immunity as an intracellular receptor initiating nuclear factor κB-dependent and mitogen-activated protein kinase-dependent gene transcription. These results demonstrated NOD2 as a novel gene involved in AgP.

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Background: Porphyromonas gingivalis is a key pathogen in microbiota associated with periodontitis. The purpose of the present study was to assess the association between salivary counts of red-complex bacteria and clinical periodontal status in a Japanese population.Methods: A total of 977 subjects who visited a general dental clinic in Japan from 2003 to 2006 were enrolled in the study. Stimulated saliva was obtained, and the amounts of major periodontal bacteria were measured using real-time polymerase chain reaction. Probing pocket depth (PPD), bleeding on probing (BOP), and each subject's average proximal bone crest level (BCL) on dental radiographs were measured. Results: The number of P. gingivalis strongly associated with percentage of 4 mm or more PPD sites, BOP positive percentage, and 1.5 mm or more BCL sites. The detection of P. gingivalis with Treponema denticola and/or Tannerella forsythia showed a high rate of three positive clinical parameters, whereas the only P. gingivalis detected group and those without P. gingivalis had a low rate of three positive clinical parameters. Conclusion: Among red-complex bacteria, the amount of P. gingivalis showed the strongest association with the severity of periodontal condition, and cooccurrence of P. gingivalis with T. denticola and/or T. forsythia showed heightened progression of periodontitis.

The association between clinically diagnosed periodontitis, a common chronic oral infection, and metabolic syndrome has been previously reported. The aim of this study was to investigate the association of plasma IgG levels against Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia, C-reactive protein, and periodontal status with metabolic syndrome. Plasma IgG levels and C-reactive protein were measured by enzyme-linked immunosorbent assay, and salivary levels of A. actinomycetemcomitans and P. gingivalis were determined by quantitative real-time polymerase chain reaction. Among 127 individuals aged 35–76 years, 57 participants had metabolic syndrome and severe periodontitis, 25 had metabolic syndrome and an absence of severe periodontitis, 17 healthy individuals had severe periodontitis, and 28 healthy individuals were without severe periodontitis. Patients with metabolic syndrome had reduced humoral immune response to A. actinomycetemcomitans (p = 0.008), regardless of their salivary levels or periodontitis status compared with healthy participants. The IgG antibody response to P. gingivalis, regardless of their salivary levels or participants’ health condition, was significantly higher in severe periodontitis patients (p<0.001). Plasma IgG titers for P. intermedia were inconsistent among metabolic syndrome or periodontal participants. Our results indicate that the presence of lower levels of IgG antibodies to A. actinomycetemcomitans (OR = 0.1; 95%CI 0.0–0.7), but not P. gingivalis, a severe periodontitis status (OR = 7.8; 95%CI 1.1–57.0), high C-reactive protein levels (OR = 9.4; 95%CI 1.0–88.2) and body mass index (OR = 3.0; 95%CI 1.7–5.2), are associated with the presence of metabolic syndrome. The role of the decreased IgG antibody response to A. actinomycetemcomitans, increased C-reactive protein levels on the association between periodontal disease and metabolic syndrome in a group of Thai patients is suggested.

Oral health screening is important for maintaining and improving quality of life. The present study aimed to determine whether patients with a certain level of alveolar bone resorption could be screened by salivary bacterial test along with their background information. Saliva samples were collected from 977 Japanese patients, and the counts of each red-complex, that is, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia, were measured using quantitative polymerase chain reaction analysis. Mean bone crest levels (BCLs) were measured using a full-mouth periapical radiograph. Multiple logistic regression analysis was used to determine associations between BCLs (1.5–4.0 mm in 0.5 mm increments) and explanatory variables, such as the number of each red-complex bacteria and the patients’ age, sex, number of teeth, stimulated saliva volume, and smoking habits. When the cutoff BCL value was set at 3.0 mm, the area under the curve, sensitivity, and specificity values were optimal at 0.86, 0.82, and 0.76, respectively. In addition, all tested explanatory variables, except sex and T. denticola count, were significantly associated with BCLs according to a likelihood ratio test (p < 0.05). Additionally, the odds ratio (OR) was substantially increased when a patient was >40 years old and the bacterial count of P. gingivalis was >107 cells/µL (OR: >6). Thus, P. gingivalis count and patients’ background information were significantly associated with the presence of a certain amount of bone resorption, suggesting that it may be possible to screen bone resorption without the need for radiography or oral examination.

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