Fusobacterium nucleatum and Tannerella forsythia Induce Synergistic Alveolar Bone Loss in a Mouse Periodontitis Model

ABSTRACTTannerella forsythiais strongly associated with chronic periodontitis, an inflammatory disease of the tooth-supporting tissues, leading to tooth loss.Fusobacterium nucleatum, an opportunistic pathogen, is thought to promote dental plaque formation by serving as a bridge bacterium between early- and late-colonizing species of the oral cavity. Previous studies have shown thatF. nucleatumspecies synergize withT. forsythiaduring biofilm formation and pathogenesis. In the present study, we showed that coinfection ofF. nucleatumandT. forsythiais more potent than infection with either species alone in inducing NF-κB activity and proinflammatory cytokine secretion in monocytic cells and primary murine macrophages. Moreover, in a murine model of periodontitis, mixed infection with the two species induces synergistic alveolar bone loss, characterized by bone loss which is greater than the additive alveolar bone losses induced by each species alone. Further, in comparison to the single-species infection, mixed infection caused significantly increased inflammatory cell infiltration in the gingivae and osteoclastic activity in the jaw bones. These data show thatF. nucleatumsubspecies andT. forsythiasynergistically stimulate the host immune response and induce alveolar bone loss in a murine experimental periodontitis model.

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Tannerella forsythia-induced Alveolar Bone Loss in Mice Involves Leucine-rich-repeat BspA Protein

Journal of Dental Research ◽

10.1177/154405910508400512 ◽

2005 ◽

Vol 84 (5) ◽

pp. 462-467 ◽

Cited By ~ 61

Author(s):

A. Sharma ◽

S. Inagaki ◽

K. Honma ◽

C. Sfintescu ◽

P.J. Baker ◽

...

Keyword(s):

Bone Loss ◽

Alveolar Bone ◽

Alveolar Bone Loss ◽

Leucine Rich Repeat ◽

Periodontal Pathogens ◽

Tannerella Forsythia ◽

Pathogenic Potential ◽

Important Virulence Factor ◽

Mouse Model Of Infection

Tannerella forsythia (formerly Bacteroides forsythus) is one of the periodontal pathogens recently implicated in the development of periodontal disease. The cell-surface-associated, as well as the secreted, leucine-rich-repeat protein (BspA) of this bacterium have been suggested to play roles in bacterial adherence, and also in inflammation, by triggering release of pro-inflammatory cytokines from monocytes and chemokines from osteoblasts, leading to inflammation and bone resorption. In this study, we sought to determine the pathogenic potential of T. forsythia and the in vivo role of the BspA protein in pathogenesis in the mouse model of infection-induced alveolar bone loss. The results showed alveolar bone loss in mice infected with the T. forsythia wild-type strain, whereas the BspA mutant was impaired. In conclusion, evidence is presented in support of T. forsythia as an important organism involved in inducing alveolar bone loss, and the BspA protein is an important virulence factor of this bacterium.

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Alveolar Bone Loss in Rats Infected With a Strain of Prevotella intermedia and Fusobacterium nucleatum Isolated From a Child With Prepubertal Periodontitis

Journal of Periodontology ◽

10.1902/jop.1997.68.1.12 ◽

1997 ◽

Vol 68 (1) ◽

pp. 12-17 ◽

Cited By ~ 4

Author(s):

Ichie Yoshida-Minami ◽

Atsuko Suzuki ◽

Keiko Kawabata ◽

Akiko Okamoto ◽

Yumi Nishihara ◽

...

Keyword(s):

Bone Loss ◽

Alveolar Bone ◽

Fusobacterium Nucleatum ◽

Alveolar Bone Loss ◽

Prevotella Intermedia

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Akkermansia muciniphila and Its Pili-Like Protein Amuc_1100 Modulate Macrophage Polarization in Experimental Periodontitis

Infection and Immunity ◽

10.1128/iai.00500-20 ◽

2020 ◽

Vol 89 (1) ◽

pp. e00500-20

Author(s):

Hannah Mulhall ◽

Jeanne M. DiChiara ◽

Matthew Deragon ◽

Radha Iyer ◽

Olivier Huck ◽

...

Keyword(s):

Bone Loss ◽

Alveolar Bone ◽

Macrophage Polarization ◽

Alveolar Bone Loss ◽

Oral Microbiome ◽

Content Type ◽

Akkermansia Muciniphila ◽

Periodontal Inflammation ◽

Experimental Periodontitis ◽

Anti Inflammatory

ABSTRACTPeriodontitis is a chronic inflammatory disease triggered by dysbiosis of the oral microbiome. Porphyromonas gingivalis is strongly implicated in periodontal inflammation, gingival tissue destruction, and alveolar bone loss through sustained exacerbation of the host response. Recently, the use of other bacterial species, such as Akkermansia muciniphila, has been suggested to counteract inflammation elicited by P. gingivalis. In this study, the effects of A. muciniphila and its pili-like protein Amuc_1100 on macrophage polarization during P. gingivalis infection were evaluated in a murine model of experimental periodontitis. Mice were gavaged with P. gingivalis alone or in combination with A. muciniphila or Amuc_1100 for 6 weeks. Morphometric analysis demonstrated that the addition of A. muciniphila or Amuc_1100 significantly reduced P. gingivalis-induced alveolar bone loss. This decreased bone loss was associated with a proresolutive phenotype (M2) of macrophages isolated from submandibular lymph nodes as observed by flow cytometry. Furthermore, the expression of interleukin 10 (IL-10) at the RNA and protein levels was significantly increased in the gingival tissues of the mice and in macrophages exposed to A. muciniphila or Amuc_1100, confirming their anti-inflammatory properties. This study demonstrates the putative therapeutic interest of the administration of A. muciniphila or Amuc_1100 in the management of periodontitis through their anti-inflammatory properties.

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HGP44 Induces Protection against Porphyromonas gingivalis-Induced Alveolar Bone Loss in Mice

Clinical and Vaccine Immunology ◽

10.1128/cvi.00556-10 ◽

2011 ◽

Vol 18 (5) ◽

pp. 888-891 ◽

Cited By ~ 5

Author(s):

Kyotaro Muramatsu ◽

Eitoyo Kokubu ◽

Takahiko Shibahara ◽

Katsuji Okuda ◽

Kazuyuki Ishihara

Keyword(s):

Bone Loss ◽

Protective Effect ◽

Porphyromonas Gingivalis ◽

Murine Model ◽

Alveolar Bone ◽

Dna Vaccines ◽

Alveolar Bone Loss ◽

Content Type ◽

Candidate Antigen

ABSTRACTThe protective effect of DNA vaccines expressing the Arg-gingipain A domain against bone loss induced byPorphyromonas gingivalisinfection was investigated in a murine model. phgp44, which expresses the 44-kDa adhesion/hemagglutinin domain of Arg-gingipain A, preventedP. gingivalis-induced alveolar bone loss. The results indicate that phgp44 could be a candidate antigen for a vaccine againstP. gingivalisinfection.

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EFFECTS OF ALENDRONATE THERAPY ON CYCLOSPORINE INDUCED ALVEOLAR BONE LOSS : A MORPHO-METRIC AND BIO-CHEMICAL STUDY IN RATS

International Journal of Advanced Research ◽

10.21474/ijar01/193 ◽

2016 ◽

Vol 4 (4) ◽

pp. 947-955

Author(s):

Sneha R Bhat ◽

◽

Aravind R Kudva ◽

Dhoom S Mehta ◽

◽

...

Keyword(s):

Bone Loss ◽

Alveolar Bone ◽

Chemical Study ◽

Alveolar Bone Loss

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3,4,5-Trihydroxybenzoic acid attenuates ligature-induced periodontal disease in Wistar rats.

Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry ◽

10.2174/1871523019666200206094335 ◽

2020 ◽

Vol 19 ◽

Author(s):

Ozkan Karatas ◽

Fikret Gevrek

Keyword(s):

Bone Loss ◽

Gallic Acid ◽

Wistar Rats ◽

Alveolar Bone ◽

Alveolar Bone Loss ◽

Collagenase Activity ◽

Osteoblastic Activity ◽

Cell Counts ◽

Experimental Periodontitis ◽

Anti Inflammatory

Background: 3,4,5-Trihydroxybenzoic acid, which is also known as gallic acid, is an anti-inflammatory agent who could provide beneficial effects in preventing periodontal inflammation. The present study aimed to evaluate the anti-inflammatory effects of gallic acid on experimental periodontitis in Wistar rats. Alveolar bone loss, osteoclastic activity, osteoblastic activity, and collagenase activity were also determined. Methods: 32 Wistar rats were used in the present study. Study groups were created as following: Healthy control (C,n=8) group; periodontitis (P,n=8) group; periodontitis and 30 mg/kg gallic acid administered group (G30,n=8); periodontitis and 60 mg/kg gallic acid administered group (G60,n=8). Experimental periodontitis was created by placing 4-0 silk sutures around the mandibular right first molar tooth. Morphological changes in alveolar bone were determined by stereomicroscopic evaluation. Mandibles were undergone histological evaluation. Matrix metalloproteinase (MMP)-8, tissue inhibitor of MMPs (TIMP)-1, bone morphogenetic protein (BMP)-2 expressions, tartrate-resistant acid phosphatase (TRAP) positive osteoclast cells, osteoblast, and inflammatory cell counts were determined. Results: Highest alveolar bone loss was observed in the periodontitis group. Both doses of gallic acid decreased alveolar bone loss compared to the P group. TRAP-positive osteoclast cell counts were higher in the P group, and gallic acid successfully lowered these counts. Osteoblast cells also increased in gallic acid administered groups. Inflammation in the P group was also higher than those of C, G30, and G60 groups supporting the role of gallic acid in preventing inflammation. 30 and 60 mg/kg doses of gallic acid decreased MMP-8 levels and increased TIMP-1 levels. BMP levels increased in gallic acid administered groups, similar to several osteoblasts. Conclusion: Present results revealed an anti-inflammatory effect of gallic acid, which was indicated by decreased alveolar bone loss and collagenase activity and increased osteoblastic activity.

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Gram-positive bacteria cell wall-derived lipoteichoic acid induces inflammatory alveolar bone loss through prostaglandin E production in osteoblasts

Scientific Reports ◽

10.1038/s41598-021-92744-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Tsukasa Tominari ◽

Ayumi Sanada ◽

Ryota Ichimaru ◽

Chiho Matsumoto ◽

Michiko Hirata ◽

...

Keyword(s):

Cell Wall ◽

Bone Loss ◽

Alveolar Bone ◽

Osteoclast Differentiation ◽

Lipoteichoic Acid ◽

Alveolar Bone Loss ◽

Gram Negative Bacteria ◽

Gram Positive ◽

Gram Negative ◽

Gram Positive Bacteria

AbstractPeriodontitis is an inflammatory disease associated with severe alveolar bone loss and is dominantly induced by lipopolysaccharide from Gram-negative bacteria; however, the role of Gram-positive bacteria in periodontal bone resorption remains unclear. In this study, we examined the effects of lipoteichoic acid (LTA), a major cell-wall factor of Gram-positive bacteria, on the progression of inflammatory alveolar bone loss in a model of periodontitis. In coculture of mouse primary osteoblasts and bone marrow cells, LTA induced osteoclast differentiation in a dose-dependent manner. LTA enhanced the production of PGE2 accompanying the upregulation of the mRNA expression of mPGES-1, COX-2 and RANKL in osteoblasts. The addition of indomethacin effectively blocked the LTA-induced osteoclast differentiation by suppressing the production of PGE2. Using ex vivo organ cultures of mouse alveolar bone, we found that LTA induced alveolar bone resorption and that this was suppressed by indomethacin. In an experimental model of periodontitis, LTA was locally injected into the mouse lower gingiva, and we clearly detected alveolar bone destruction using 3D-μCT. We herein demonstrate a new concept indicating that Gram-positive bacteria in addition to Gram-negative bacteria are associated with the progression of periodontal bone loss.

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