Ligature‐associated bacterial profiles are linked to type 2 diabetes mellitus in a rat model and influenced by antibody treatment against TNF‐α or RAGE

Grauballe, Morten Bay; Belstrøm, Daniel; Østergaard, Jakob Appel; Paster, Bruce J.; Schou, Søren; Flyvbjerg, Allan; Holmstrup, Palle

doi:10.1002/cre2.54

Cited by 5 publications

(3 citation statements)

References 34 publications

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“…Moreover, the characteristics of the disease in nonhuman primates, including Macaca fascicularis, Macaca mulatta, Macaca nemestrina, and Papio anubis, display features of naturally occurring human disease, such as the general lack of disease in younger individuals and an increased extent and severity of disease with aging (49)(50)(51)(52). Additionally, this model has been extensively used to evaluated the kinetics and progression of disease using a ligature-induced periodontitis model (53) that has been adapted to rodents (54,55) and rabbits (56). However, to more fully examine the microbiome changes that occur with disease initiation and progression, only nonhuman primates provide a "microbiomic" analogy to humans.…”

Section: Discussionmentioning

confidence: 99%

Microbiome Profiles of Ligature-Induced Periodontitis in Nonhuman Primates across the Life Span

Kirakodu

Chen

Martinez³

et al. 2019

Infect Immun

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This investigation compared the microbiomes colonizing teeth during the initiation, progression, and resolution of periodontitis in nonhuman primates (Macaca mulatta) at different ages. Subgingival plaque samples were collected at baseline; 0.5, 1, and 3 months following ligature-induced periodontitis; and following naturally occurring disease resolution at 5 months. Samples were analyzed using 16S amplicon sequencing to identify bacterial profiles across age groups: young (<3 years of age), adolescent (3 to 7 years), adult (12 to 15 years), and aged (17 to 23 years). α-Diversity of the microbiomes was greater in the adult/aged samples than in the young/adolescent samples. β-Diversity of the samples demonstrated clear age group differences, albeit individual variation in microbiomes between animals within the age categories was noted. Phylum distributions differed between the young/adolescent animals and the adult/aged animals at each of the time points, showing an enrichment of the phyla Spirochetes, Fusobacteria, and Bacteroidetes associated with periodontitis. Major differences in the top 50 operational taxonomic units (OTUs) were noted in the young and adolescent microbiomes during initiation and progression postligation compared to the adult and aged animals. The proportions of a large number of species in the top 50 OTUs were lower at baseline and in resolved disease microbiomes in the young samples, while profiles in adolescent animals were more consistent with the disease microbiomes. Microbiome profiles for resolution for adults and aged animals appeared more resilient and generally maintained a pattern similar to that of disease. Use of the model can expand our understanding of the crucial interactions of the oral microbiome and host responses in periodontitis.

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Section: Discussionmentioning

confidence: 99%

Microbiome Profiles of Ligature-Induced Periodontitis in Nonhuman Primates across the Life Span

Kirakodu

Chen

Martinez³

et al. 2019

Infect Immun

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“…This study indicates that blocking TNF- α improves the metabolic status in obese rats with PD and decreases periodontal breakdown associated with diabetes. The same research group also confirmed that anti-TNF- α treatment positively impacts the subgingival microbial profile in rats with diabetes and ligature-induced bone loss [ 116 ]. Another study investigated anti-TNF- α effects with pentoxifylline in an experimental mouse model of chronic antigen-induced arthritis- (AIA-) associated PD [ 117 ].…”

Section: Biological Therapiesmentioning

confidence: 86%

Pharmacological Therapies for the Management of Inflammatory Bone Resorption in Periodontal Disease: A Review of Preclinical Studies

Pavanelli

Menezes

Pereira

et al. 2022

BioMed Research International

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Periodontitis, a highly prevalent multicausal chronic inflammatory and destructive disease, develops as a result of complex host-parasite interactions. Dysbiotic bacterial biofilm in contact with the gingival tissues initiates a cascade of inflammatory events, mediated and modulated by the host’s immune response, which is characterized by increased expression of several inflammatory mediators such as cytokines and chemokines in the connective tissue. If periodontal disease (PD) is left untreated, it results in the destruction of the supporting tissues around the teeth, including periodontal ligament, cementum, and alveolar bone, which lead to a wide range of disabilities and poor quality of life, thus imposing significant burdens. This process depends on the differentiation and activity of osteoclasts, the cells responsible for reabsorbing the bone tissue. Therefore, the inhibition of differentiation or activity of these cells is a promising strategy for controlling bone resorption. Several pharmacological drugs that target osteoclasts and inflammatory cells with immunomodulatory and anti-inflammatory effects, such as bisphosphonates, anti-RANK-L antibody, strontium ranelate, cathepsin inhibitors, curcumin, flavonoids, specialized proresolving mediators, and probiotics, were already described to manage inflammatory bone resorption during experimental PD progression in preclinical studies. Meantime, a growing number of studies have described the beneficial effects of herbal products in inhibiting bone resorption in experimental PD. Therefore, this review summarizes the role of several pharmacological drugs used for PD prevention and treatment and highlights the targeted action of all those drugs with antiresorptive properties. In addition, our review provides a timely and critical appraisal for the scientific rationale use of the antiresorptive and immunomodulatory medications in preclinical studies, which will help to understand the basis for its clinical application.

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“…A limitation of this study was that ligatures were used to induce EP. Although EP represents a relatively acute model, the ligatures increased the colonization of bacteria and shifts the sub‐gingival microbiota (Grauballe et al, 2017; C. T. Lee, Teles, et al, 2016; Xiao et al, 2017), mimicking the microbial dysbiosis in periodontitis patients to some extent. Other models such as LPS injection or periodontal bacteria oral gavage can be used as alternatives.…”

Section: Discussionmentioning

confidence: 99%

Selective BET inhibitor RVX‐208 ameliorates periodontal inflammation and bone loss

Sun,

Clayton,

Alam

et al. 2023

J Clinic Periodontology

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AimTo determine the effects of RVX‐208, a selective bromodomain and extra‐terminal domain (BET) inhibitor targeting bromodomain 2 (BD2), on periodontal inflammation and bone loss.Materials and MethodsMacrophage‐like cells (RAW264.7) and human gingival epithelial cells were challenged by Porphyromonas gingivalis (Pg) with or without RVX‐208. Inflammatory gene expression and cytokine production were measured by reverse transcription polymerase chain reaction and enzyme‐linked immunosorbent assay, respectively. RAW264.7 cells were induced to osteoclast differentiation. After RVX‐208 treatment, osteoclast differentiation was evaluated by histology, tartrate‐resistant‐acid‐phosphatase (TRAP) activity and the expression of osteoclast‐specific genes. The effect of RVX‐208 on osteoclast transcriptome was studied by RNA sequencing. Periodontitis was induced in rats by ligature and local RVX‐208 treatment was administered every other day. Alveolar bone loss was measured by micro‐computed tomography.ResultsRVX‐208 inhibited inflammatory gene expression and cytokine production in Pg‐infected cells. Osteoclast differentiation was inhibited by RVX‐208, as evidenced by reduced osteoclast number, TRAP activity and osteoclast‐specific gene expression. RVX‐208 displayed a more selective and less profound suppressive impact on transcriptome compared with pan‐BET inhibitor, JQ1. RVX‐208 administration prevented the alveolar bone loss in vivo.ConclusionsRVX‐208 regulated both upstream (inflammatory cytokine production) and downstream (osteoclast differentiation) events that lead to periodontal tissue destruction, suggesting that it may be a promising ‘epi‐drug’ for the prevention of periodontitis.

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Ligature‐associated bacterial profiles are linked to type 2 diabetes mellitus in a rat model and influenced by antibody treatment against TNF‐α or RAGE

Cited by 5 publications

References 34 publications

Microbiome Profiles of Ligature-Induced Periodontitis in Nonhuman Primates across the Life Span

Microbiome Profiles of Ligature-Induced Periodontitis in Nonhuman Primates across the Life Span

Pharmacological Therapies for the Management of Inflammatory Bone Resorption in Periodontal Disease: A Review of Preclinical Studies

Selective BET inhibitor RVX‐208 ameliorates periodontal inflammation and bone loss

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