Receptor activator of nuclear factor kappa B ligand antagonists inhibit tissue inflammation and bone loss in experimental periodontitis

Yuan, Huaiping; Gupte, Rohit; Zelkha, Sami; Amar, Salomon

doi:10.1111/j.1600-051x.2011.01780.x

Cited by 45 publications

(52 citation statements)

References 34 publications

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“…Furthermore, considerable numbers of RANKL-expressing cells were found in the bone-surrounding gingiva, in particular CD4 + T cells, which resulted in enhanced destruction of alveolar bone. Our results are in line with the well-established role of RANK-RANKL interactions, CD4 + T cells, and IFN-γ during experimental periodontitis, the model used in the present study (9,(13)(14)(15).…”

Section: Discussionsupporting

confidence: 91%

Langerhans cells down-regulate inflammation-driven alveolar bone loss

Arizon

Nudel

Segev

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Excessive bone resorption is frequently associated with chronic infections and inflammatory diseases. Whereas T cells were demonstrated to facilitate osteoclastogenesis in such diseases, the role of dendritic cells, the most potent activators of naive T cells, remains unclear. Using a model involving inflammation-driven alveolar bone loss attributable to infection, we showed that in vivo ablation of Langerhans cells (LCs) resulted in enhanced bone loss. An increased infiltration of B and T lymphocytes into the tissue surrounding the bone was observed in LC-ablated mice, including receptor activator of NF-κB ligand (RANKL)-expressing CD4 + T cells with known capabilities of altering bone homeostasis. In addition, the absence of LCs significantly reduced the numbers of CD4 + Foxp3 + T-regulatory cells in the tissue. Further investigation revealed that LCs were not directly involved in presenting antigens to T cells. Nevertheless, despite their low numbers in the tissue, the absence of LCs resulted in an elevated activation of CD4 + but not CD8 + T cells. This activation involved elevated production of IFN-γ but not IL-17 or IL-10 cytokines. Our data, thus, reveal a protective immunoregulatory role for LCs in inflammation-induced alveolar bone resorption, by inhibiting IFN-γ secretion and excessive activation of RANKL + CD4 + T cells with a capability of promoting osteoclastogenesis.

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Section: Discussionsupporting

confidence: 91%

Langerhans cells down-regulate inflammation-driven alveolar bone loss

Arizon

Nudel

Segev

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…A very similar distribution pattern of polymorphonuclear leukocyte (PMN) and mononuclear cell (MN) infiltration was noted throughout the three interdental areas of interest, boxes 1, 2, and 3 ( Fig. S1 shows anatomical landmarks and describes the boxes) (27), over time in all groups ( Fig. 2 B-D).…”

Section: Apoementioning

confidence: 73%

Pivotal role of NOD2 in inflammatory processes affecting atherosclerosis and periodontal bone loss

Yuan¹,

Zelkha²,

Burkatovskaya³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Significance Apolipoprotein E −/− (ApoE −/− ) mice deficient in nucleotide binding oligomerization domain-containing protein 2 (NOD2) and subjected to an oral gavage of Porphyromonas gingivalis developed elevated serum inflammatory cytokines, cholesterol, alveolar bone loss, and atherosclerosis. Stimulation of NOD2 by Muramyl DiPeptide (MDP) in ApoE −/− mice reduced P. gingivalis -induced inflammatory cytokines, cholesterol, alveolar bone loss, and atherosclerosis by reducing the expression of inhibitor of NF-κB kinase-β, NF-κB, JNK mRNA, and TNF-α protein levels. A reduction in body weight gain was observed in ApoE −/− mice fed a high-fat diet (HFD) and injected with MDP compared to ApoE −/− mice fed a HFD but saline injected. MDP activation of NOD2 should be considered in the treatment of inflammatory processes affecting atherosclerosis, bone loss, and possibly, weight gain.

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“…Blue arrows point to alveolar bone crest, black double arrows to the distance from CEJ to ABC, red arrows to areas of inflammation, and green arrows to areas of bone resorption junctional epithelium, increase in the number of inflammatory cells in the connective tissue, periodontal ligament fiber loss, and alveolar bone resorption [18,[23][24][25]. The inoculation of human bacterial strains by oral gavage has been studied in various mice models [7,9,30,31,34,35,48], and it is used to examine the impact of bacteria and their pathogenassociated molecular patterns (PAMPS) on various components of the host response. Also, this model has been used in an attempt to reproduce the alveolar bone resorption observed during chronic human PD.…”

Section: Discussionmentioning

confidence: 99%

Long-term evaluation of oral gavage with periodontopathogens or ligature induction of experimental periodontal disease in mice

et al. 2015

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The ligature model was an effective approach to induce inflammation and bone loss similar to human periodontitis, but the oral gavage models were not efficient in inducing periodontal inflammation and tissue destruction in the conditions studied. Ligature models can provide a basis for future interventional studies that contribute to the understanding of the disease pathogenesis and the complex host response to microbial challenge.

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Receptor activator of nuclear factor kappa B ligand antagonists inhibit tissue inflammation and bone loss in experimental periodontitis

Cited by 45 publications

References 34 publications

Langerhans cells down-regulate inflammation-driven alveolar bone loss

Langerhans cells down-regulate inflammation-driven alveolar bone loss

Pivotal role of NOD2 in inflammatory processes affecting atherosclerosis and periodontal bone loss

Long-term evaluation of oral gavage with periodontopathogens or ligature induction of experimental periodontal disease in mice

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