Gingival solitary chemosensory cells are immune sentinels for periodontitis

Abstract Solitary chemosensory cells (SCCs) are epithelial sentinels that utilize bitter Tas2r receptors and coupled taste transduction elements to detect pathogenic bacterial metabolites, triggering host defenses to control the infection. Here we report that SCCs are present in mouse gingival junctional epithelium, where they express several Tas2rs and the taste signaling components α-gustducin (Gnat3), TrpM5, and Plcβ2. Gnat3−/− mice have altered commensal oral microbiota and accelerated naturally occurring alveolar bone loss. In ligature-induced periodontitis, knockout of taste signaling molecules or genetic absence of gingival SCCs (gSCCs) increases the bacterial load, reduces bacterial diversity, and renders the microbiota more pathogenic, leading to greater alveolar bone loss. Topical treatment with bitter denatonium to activate gSCCs upregulates the expression of antimicrobial peptides and ameliorates ligature-induced periodontitis in wild-type but not in Gnat3−/− mice. We conclude that gSCCs may provide a promising target for treating periodontitis by harnessing innate immunity to regulate the oral microbiome.

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Effects of Colocasia antiquorum var. Esculenta Extract In Vitro and In Vivo against Periodontal Disease

Medicina ◽

10.3390/medicina57101054 ◽

2021 ◽

Vol 57 (10) ◽

pp. 1054

Author(s):

Seong-Hee Moon ◽

Seong-Jin Shin ◽

Hyun-Jin Tae ◽

Seung-Han Oh ◽

Ji-Myung Bae

Keyword(s):

Bone Loss ◽

Periodontal Disease ◽

Pathogenic Bacteria ◽

Alveolar Bone ◽

Negative Control ◽

Alveolar Bone Loss ◽

Oral Microbiome ◽

Control Group

Background and Objectives: Periodontal disease is a chronic inflammatory disease in which gradual destruction of tissues around teeth is caused by plaque formed by pathogenic bacteria. The purpose of this study was to evaluate the potential of 75% ethanol extract of Colocasia antiquorum var. esculenta (CA) as a prophylactic and improvement agent for periodontal disease in vitro and in vivo. Materials and Methods: The antimicrobial efficacy of CA against Porphyromonas gingivalis (P. gingivalis, ATCC 33277) was evaluated using minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) test, and cytotoxicity was confirmed by CCK-8 assay. For the in vivo study, P. gingivalis was applied by oral gavage to BALB/c mice. Forty-two days after the first inoculation of P. gingivalis, intraoral swabs were taken for microbiome analysis, and the mice were sacrificed to evaluate the alveolar bone loss. Results: The MIC of CA against P. gingivalis was 31.3 μg/mL, the MBC was 62.5 μg/mL, with no cytotoxicity. The diversity of the oral microbiome decreased in the positive control group, while those of the VA (varnish) and VCA (varnish added with CA) groups increased as much as in the negative control group, although the alveolar bone loss was not induced in the mouse model. Conclusions: CA showed antibacterial effects in vitro, and the VA and VCA groups exhibited increased diversity in the oral microbiome, suggesting that CA has potential for improving periodontal disease.

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Arthritis-induced alveolar bone loss is associated with changes in the composition of oral microbiota

Anaerobe ◽

10.1016/j.anaerobe.2016.03.006 ◽

2016 ◽

Vol 39 ◽

pp. 91-96 ◽

Cited By ~ 14

Author(s):

Jôice Dias Corrêa ◽

Adriana Machado Saraiva ◽

Celso Martins Queiroz-Junior ◽

Mila Fernandes Moreira Madeira ◽

Poliana Mendes Duarte ◽

...

Keyword(s):

Bone Loss ◽

Alveolar Bone ◽

Alveolar Bone Loss ◽

Oral Microbiota

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Bifidobacterium Strains Present Distinct Effects on the Control of Alveolar Bone Loss in a Periodontitis Experimental Model

Frontiers in Pharmacology ◽

10.3389/fphar.2021.713595 ◽

2021 ◽

Vol 12 ◽

Author(s):

Natali Shimabukuro ◽

Amália C. de S. Cataruci ◽

Karin H. Ishikawa ◽

Bruna E. de Oliveira ◽

Dione Kawamoto ◽

...

Keyword(s):

Bone Loss ◽

Alveolar Bone ◽

Microbial Consortium ◽

Bone Destruction ◽

Experimental Period ◽

Serum Levels ◽

Alveolar Bone Loss ◽

Oral Microbiome ◽

Host Cells ◽

Tnf Α

Periodontitis is an inflammatory disease induced by a dysbiotic oral microbiome. Probiotics of the genus Bifidobacterium may restore the symbiotic microbiome and modulate the immune response, leading to periodontitis control. We evaluated the effect of two strains of Bifidobacterium able to inhibit Porphyromonas gingivalis interaction with host cells and biofilm formation, but with distinct immunomodulatory properties, in a mice periodontitis model. Experimental periodontitis (P+) was induced in C57Bl/6 mice by a microbial consortium of human oral organisms. B. bifidum 1622A [B+ (1622)] and B. breve 1101A [B+ (1101)] were orally inoculated for 45 days. Alveolar bone loss and inflammatory response in gingival tissues were determined. The microbial consortium induced alveolar bone loss in positive control (P + B-), as demonstrated by microtomography analysis, although P. gingivalis was undetected in oral biofilms at the end of the experimental period. TNF-α and IL-10 serum levels, and Treg and Th17 populations in gingiva of SHAM and P + B- groups did not differ. B. bifidum 1622A, but not B. breve 1101A, controlled bone destruction in P+ mice. B. breve 1101A upregulated transcription of Il-1β, Tnf-α, Tlr2, Tlr4, and Nlrp3 in P-B+(1101), which was attenuated by the microbial consortium [P + B+(1101)]. All treatments downregulated transcription of Il-17, although treatment with B. breve 1101A did not yield such low levels of transcripts as seen for the other groups. B. breve 1101A increased Th17 population in gingival tissues [P-B+ (1101) and P + B+ (1101)] compared to SHAM and P + B-. Administration of both bifidobacteria resulted in serum IL-10 decreased levels. Our data indicated that the beneficial effect of Bifidobacterium is not a common trait of this genus, since B. breve 1101A induced an inflammatory profile in gingival tissues and did not prevent alveolar bone loss. However, the properties of B. bifidum 1622A suggest its potential to control periodontitis.

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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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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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