scholarly journals Periodontal dysbiosis linked to periodontitis is associated with cardiometabolic adaptation to high-fat diet in mice

2016 ◽  
Vol 310 (11) ◽  
pp. G1091-G1101 ◽  
Author(s):  
Maxime Branchereau ◽  
François Reichardt ◽  
Pascale Loubieres ◽  
Pauline Marck ◽  
Aurélie Waget ◽  
...  
Keyword(s):  
Bone Loss ◽  
High Fat Diet ◽  
Alveolar Bone ◽  
Alveolar Bone Loss ◽  
Metabolic Adaptation ◽  
Mrna Levels ◽  
Periodontal Pathogens ◽  
High Fat ◽  
Cardiac Phenotype ◽  
Periodontal Inflammation

Periodontitis and type 2 diabetes are connected pandemic diseases, and both are risk factors for cardiovascular complications. Nevertheless, the molecular factors relating these two chronic pathologies are poorly understood. We have shown that, in response to a long-term fat-enriched diet, mice present particular gut microbiota profiles related to three metabolic phenotypes: diabetic-resistant (DR), intermediate (Inter), and diabetic-sensitive (DS). Moreover, many studies suggest that a dysbiosis of periodontal microbiota could be associated with the incidence of metabolic and cardiac diseases. We investigated whether periodontitis together with the periodontal microbiota may also be associated with these different cardiometabolic phenotypes. We report that the severity of glucose intolerance is related to the severity of periodontitis and cardiac disorders. In detail, alveolar bone loss was more accentuated in DS than Inter, DR, and normal chow-fed mice. Molecular markers of periodontal inflammation, such as TNF-α and plasminogen activator inhibitor-1 mRNA levels, correlated positively with both alveolar bone loss and glycemic index. Furthermore, the periodontal microbiota of DR mice was dominated by the Streptococcaceae family of the phylum Firmicutes, whereas the periodontal microbiota of DS mice was characterized by increased Porphyromonadaceae and Prevotellaceae families. Moreover, in DS mice the periodontal microbiota was indicated by an abundance of the genera Prevotella and Tannerella, which are major periodontal pathogens. PICRUSt analysis of the periodontal microbiome highlighted that prenyltransferase pathways follow the cardiometabolic adaptation to a high-fat diet. Finally, DS mice displayed a worse cardiac phenotype, percentage of fractional shortening, heart rhythm, and left ventricle weight-to-tibia length ratio than Inter and DR mice. Together, our data show that periodontitis combined with particular periodontal microbiota and microbiome is associated with metabolic adaptation to a high-fat diet related to the severity of cardiometabolic alteration.

High‐Fat Diet‐Induced Metabolic Syndrome Increases Ligature‐Induced Alveolar Bone Loss in Mice

Oral Diseases ◽  
2021 ◽  
Author(s):  
Zhongyang Lu ◽  
Yanchun Li ◽  
Hong Yu ◽  
Maria F. Lopes‐Virella ◽  
Yan Huang
Keyword(s):  
Metabolic Syndrome ◽  
Bone Loss ◽  
High Fat Diet ◽  
Alveolar Bone ◽  
Alveolar Bone Loss ◽  
High Fat

Angiopoietin‐like protein 2 deficiency promotes periodontal inflammation and alveolar bone loss

2021 ◽  
Author(s):  
Chenxi Jiang ◽  
Siqi Yao ◽  
Yi Guo ◽  
Li Ma ◽  
Xiaoxuan Wang ◽  
...  
Keyword(s):  
Bone Loss ◽  
Alveolar Bone ◽  
Alveolar Bone Loss ◽  
Periodontal Inflammation

scholarly journals Resolution phase agonists &bone remodeling

2016 ◽  
Author(s):  
Ευάγγελος Παπαθανασίου
Keyword(s):  
Bone Loss ◽  
Alveolar Bone ◽  
Peritoneal Macrophages ◽  
Alveolar Bone Loss ◽  
Cytokine Signaling ◽  
Periodontal Inflammation ◽  
Oral Inoculation ◽  
Tnf Α ◽  
Socs Proteins ◽  
Anti Inflammatory

Periodontitis is the 6th most prevalent disease in the world and the primary cause for tooth loss in adults. The host immune response plays a key role in bacteria-induced alveolar bone resorption. Endogenous control of the magnitude and duration of inflammatory signaling is considered an important determinant of the extent of periodontal pathology. Suppressor of cytokine signaling (SOCS) proteins are inhibitors of cytokine signaling pathways and may play a role in controlling periodontal inflammation. SOCS proteins are also considered crucial intracellular mediators of the anti-inflammatory actions of lipid mediator agonists including resolvins such as RvE1. We hypothesized that SOCS-3 regulates inflammatory cytokine signaling and alveolar bone loss in experimental periodontitis and that the anti-inflammatory actions of RvE1 are SOCS-3 dependent. Periodontal bone loss was induced in myeloid-specific SOCS-3-knockout (KO) and SOCS-3-wild-type (WT) C57Bl6-B.129 mice by oral inoculation with 1×109 colony-forming units (CFU) P. gingivalis A7436 using an oral gavage model for periodontitis. Sham controls for both types of mice received vehicle without bacteria. The mice were euthanized 6 weeks after the last oral inoculation. Morphometric, histomorphometric, and µCT analyses were performed to assess alveolar bone loss. Peritoneal macrophages were elicited with 4% thioglycolate broth and isolated from myeloid SOCS-3-KO and SOCS-3-WT mice by differential centrifugation. Macrophages were cultured at a concentration of 1.5×106 cells/ml in 6-well plates. After 2 hours, non-adherent cells were discarded and the remaining adherent cells were treated with either culture medium alone (control) or with 100 ng/ml P. gingivalis A7436 LPS or with culture medium and 100nM RvE1 or with 100 ng/ml P. gingivalis A7436 LPS and RvE1 100nM (n≥3 wells per group). Supernatants and cells were collected after 12 hours. Cytokine levels were assessed using Luminex multiplex bead immunoassay and RNA was extracted by Trizol and processed for qRT-PCR. Increased bone loss was demonstrated in P. gingivalis-infected SOCS-3- KO mice compared to P. gingivalis-infected WT mice by direct morphological measurements, µCT analyses and quantitative histology. Loss of SOCS-3 function resulted in increased number of alveolar bone osteoclasts and increased RANKL expression after P. gingivalis infection. SOCS-3 deficiency in myeloid cells also promoted a higher P. gingivalis LPS-induced inflammatory response by inducing a higher secretion of IL-1β, IL-6, TNF-α and KC (IL-8) by peritoneal macrophages from SOCS-3-KO mice. 100nM RvE1 resulted in a significant decrease in P. gingivalis LPS-induced secretion of IL-6, TNF-α and IL-8 by increasing mRNA expression of SOCS-3 and ERV1 in macrophages from SOCS-3-WT mice compared to macrophages from myeloid SOCS-3-KO ones. Our data implicate SOCS-3 as a critical negative regulator of alveolar bone loss in experimental periodontitis and P. gingivalis LPS-induced inflammatory response. SOCS-3 regulates the anti-inflammatory actions of RvE1 on P. gingivalis LPS-induced inflammatory cytokines in macrophages. Understanding further the role of SOCS proteins in regulating periodontal inflammation may provide novel pathways of host susceptibility to periodontitis and new therapeutic targets for modulating the immune response to achieve successful resolution of periodontal inflammation.

scholarly journals Mixed lineage kinase domain-like pseudokinase mediated necroptosis aggravates periodontitis progression

2021 ◽  
Author(s):  
Yanan Yang ◽  
Lingxia Wang ◽  
Haibing Zhang ◽  
Lijun Luo
Keyword(s):  
Bone Marrow ◽  
Bone Loss ◽  
Porphyromonas Gingivalis ◽  
Alveolar Bone ◽  
Alveolar Bone Loss ◽  
Mrna Levels ◽  
Genetic Ablation ◽  
Osteoclast Activation

Abstract Necroptosis is a form of cell death that is reportedly involved in the pathogenesis of periodontitis. However, the role of Mlkl-involved necroptosis remains unclear. Herein, we aim to explore the role of MLKL-mediated necroptosis in periodontitis in vitro and in vivo. Expression of RIPK3, MLKL, and phosphorylated MLKL is observed in gingival tissues obtained from healthy subjects or patients with periodontitis. Viability of Porphyromonas gingivalis lipopolysaccharide (LPS-Pg)-treated cells was detected. In wild type or Mlkl deficiency mice with ligature-induced periodontitis, alveolar bone loss and osteoclast activation were assessed. mRNA levels of inflammatory cytokines in bone marrow-derived macrophages were tested by qRT-PCR. Increased expression of RIPK3, MLKL, and phosphorylated MLKL is observed in gingival tissues obtained from patients with periodontitis. Porphyromonas gingivalis lipopolysaccharide (LPS-Pg)-treated cells developed necroptosis after caspase inhibition and negatively regulated the NF-κB signaling pathway. In mice with ligature-induced periodontitis, Mlkl deficiency reduced alveolar bone loss and weakened osteoclast activation. Furthermore, genetic ablation of Mlkl in LPS-Pg-treated bone marrow-derived macrophages increased the mRNA levels of tumor necrosis factor-α, interleukin (Il)-1β, Il-6, cyclooxygenase 2, matrix metalloproteinase 9, and receptor activator of nuclear factor kappa-B ligand. Our data indicated that MLKL-mediated necroptosis aggravates the development of periodontitis in a Mlkl-deficient mouse. And this will provide a new sight for the understanding of etiology and therapies of periodontitis.

scholarly journals Periodontal pathogens alter the synovial proteome. Periodontal pathogens do not exacerbate macroscopic arthritis but alter the synovial proteome in mice

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0242868
Author(s):  
Anna-Lena Buschhart ◽  
Lennart Bolten ◽  
Johann Volzke ◽  
Katharina Ekat ◽  
Susanne Kneitz ◽  
...  
Keyword(s):  
Bone Loss ◽  
Alveolar Bone ◽  
Inflammatory Diseases ◽  
Expression Patterns ◽  
Therapy Response ◽  
Alveolar Bone Loss ◽  
Periodontal Pathogens ◽  
Pathogenic Potential ◽  
Humoral Immune ◽  
Set Up

Rheumatoid arthritis (RA) and periodontitis (PD) are chronic inflammatory diseases that appear to occur in tandem. However, the mutual impact PD exerts on RA and vice versa has not yet been defined. To address this issue, we set up an animal model and analyzed how two prime inducers of periodontitis—Porphyromonas gingivalis (Pg) and Aggregatibacter actinomycetemcomitans (Aa)–differ in their pathogenic potential. Our experimental setup included collagen induced arthritis (CIA) in the mouse, oral inoculation with Pg or Aa to induce alveolar bone loss and the combination of both diseases in inverted orders of events. Neither pathobiont impacted on macroscopic arthritis and arthritis did not exacerbate alveolar bone loss. However, there were subtle differences between Pg and Aa with the former inducing more alveolar bone loss if PD was induced before CIA. On a molecular level, Pg and Aa led to differential expression patterns in the synovial membranes that were reminiscent of cellular and humoral immune responses, respectively. The Pg and Aa specific signatures in the synovial proteomes suggest a role for oral pathogens in shaping disease subtypes and setting the stage for subsequent therapy response.

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

2005 ◽  
Vol 84 (5) ◽  
pp. 462-467 ◽  
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.

scholarly journals Involvement of SOCS3 in Regulation of CD11c+ Dendritic Cell-Derived Osteoclastogenesis and Severe Alveolar Bone Loss

2009 ◽  
Vol 77 (5) ◽  
pp. 2000-2009 ◽  
Author(s):  
Xiaoxia Zhang ◽  
Mawadda Alnaeeli ◽  
Bhagirath Singh ◽  
Yen-Tung A. Teng
Keyword(s):  
T Cells ◽  
Dendritic Cell ◽  
Bone Loss ◽  
Alveolar Bone ◽  
Expression Profiles ◽  
Critical Role ◽  
Alveolar Bone Loss ◽  
Cytokine Signaling ◽  
Periodontal Inflammation ◽  
Socs3 Expression

ABSTRACT To investigate the role of suppressor of cytokine signaling (SOCS) molecules in periodontal immunity and RANKL-mediated dendritic cell (DC)-associated osteoclastogenesis, we analyzed SOCS expression profiles in CD4+ T cells and the effect of SOCS3 expression in CD11c+ DCs during periodontal inflammation-induced osteoclastogenesis and bone loss in nonobese diabetic (NOD) versus humanized NOD/SCID mice. Our results of ex vivo and in vitro analyses showed that (i) there is significantly higher SOCS3 expression associated with RANKL+ T-cell-mediated bone loss in correlation with increased CD11c+ DC-mediated osteoclastogenesis; (ii) the transfection of CD11c+ DC using an adenoviral vector carrying a dominant negative SOCS3 gene significantly abrogates TRAP and bone-resorptive activity; and (iii) inflammation-induced TRAP expression, bone resorption, and SOCS3 activity are not associated with any detectable change in the expression levels of TRAF6 and mitogen-activated protein kinase signaling adaptors (i.e., Erk, Jnk, p38, and Akt) in RANKL+ T cells. We conclude that SOCS3 plays a critical role in modulating cytokine signaling involved in RANKL-mediated DC-derived osteoclastogenesis during immune interactions with T cells and diabetes-associated severe inflammation-induced alveolar bone loss. Therefore, the development of SOCS3 inhibitors may have therapeutic potential as the target to halt inflammation-induced bone loss under pathological conditions in vivo.

Cinnamic acid decreases periodontal inflammation and alveolar bone loss in experimental periodontitis

2020 ◽  
Vol 55 (5) ◽  
pp. 676-685
Author(s):  
Ozkan Karatas ◽  
Hatice Balci Yuce ◽  
Mehmet Murat Taskan ◽  
Fikret Gevrek ◽  
Cemil Alkan ◽  
...  
Keyword(s):  
Bone Loss ◽  
Cinnamic Acid ◽  
Alveolar Bone ◽  
Alveolar Bone Loss ◽  
Periodontal Inflammation ◽  
Experimental Periodontitis
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