Expression cloning of a periodontitis-associated apoptotic effector, cagE homologue, in Actinobacillus actinomycetemcomitans

Teng, Yen-Tung A.; Hu, Wenqi

doi:10.1016/s0006-291x(03)00471-6

Cited by 27 publications

(41 citation statements)

References 42 publications

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“…Later, horseradish peroxidase-or allophycocyanin-conjugated anti-mouse or rabbit/rat IgG was used as secondary Ab at a 1/2,000 dilution (47,48). Bound protein complexes were detected with the enhanced chemiluminescence kit (Amersham) and then visualized with the Kodak-2000 mm Image Station for quantification and comparisons (50,51). The results of our pilot immunoblot assays suggested that the antibodies used here were specific and did not cross-react or bind nonspecifically to the target molecules (data not shown).…”

Section: Vol 77 2009 Socs3 Modulates Alveolar Bone Loss 2001mentioning

confidence: 90%

“…We previously showed that the inflammatory cytokine IFN-␥ is coexpressed with RANKL in A. actinomycetemcomitans-reactive CD4 ϩ T cells, where it positively modulates osteoclastogenesis and enhances active alveolar bone loss in vivo (54). This phenomenon was also evident in A. actinomycetemcomitans-associated alveolar bone loss mediated by a potent proapoptotic antigen (i.e., CagE homologue) (50,51), which induces robust IFN-␥ expression in microbe-specific RANKL ϩ Th1 cells (27,54). In contrast, IL-10 in our model exerts an antiinflammatory effect by downregulating RANKL-mediated osteoclastogenesis both in vivo and in vitro, suggesting that there is a network of regulatory interactions between RANKL and immune cytokines in the periodontium (53,63).…”

Section: Expression Of a Dominant-negative Form Of The Socs3 Gene In mentioning

confidence: 94%

“…To quantify protein expression, immunoblot assays were employed as described previously (50,51). Briefly, the cells/tissues were homogenized in lysis buffer (20 mM Tris HCl, pH 7.4, 150 mM NaCl, 0.5% Triton X-100, 100 M sodium vanadate, 1 mM dithiothreitol, 5 mg/ml leupeptin, 1 mM phenylmethylsulfonyl fluoride, and protease inhibitor cocktail; Roche Applied Science) and cleared by centrifugation at 15,000 ϫ g at 4°C for 15 min.…”

Section: Vol 77 2009 Socs3 Modulates Alveolar Bone Loss 2001mentioning

confidence: 99%

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

et al. 2009

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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.Inflammatory bone diseases affect a large portion of the skeletal system, particularly those portions underlying mucosal surfaces, where inflammation-induced bone loss is closely associated with elevated osteoclast (OC) activity (15, 48). Inflammation-induced bone loss is readily manifested in periodontal disease (i.e., periodontitis), resulting in attachments loss, including periodontal connective tissues and supporting alveolar bone, as a consequence of the interplays between the specific subgingival biofilm and the host's immune/inflammatory responses (36, 37). The tumor necrosis factor (TNF) family member receptor activator of NF-B ligand (RANKL), its receptor, RANK, and the natural antagonist, osteoprotegrin (OPG), have been shown to be the key regulators of the differentiation, activation, and survival of OCs and OC. precursors (5,[16][17][18][23][24][25]44,55,58). In addition, it is now clear that the host responses, especially T-cell immunity, play a pivotal role in regulating osteoclastogenesis and homeostasis of the bone tissues (termed osteoimmunology [5]). Activated CD4 ϩ T cells express RANKL, which can directly trigger osteoclastogenesis and bone loss, and they can also negatively regulate RANKL activity via OPG production. For instance, it has been shown that OPG treatment results in significantly reduced bone loss in arthritis, osteoporosis, and cancer-related bone metastasis (16-18, 24, 45, 48, 55, 58). In murine models of periodontitis, OPG injections yield a robust inhibition of alveolar bone loss of up to 80 to 100%, suggesting that the R...

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Section: Vol 77 2009 Socs3 Modulates Alveolar Bone Loss 2001mentioning

confidence: 90%

Section: Expression Of a Dominant-negative Form Of The Socs3 Gene In mentioning

confidence: 94%

Section: Vol 77 2009 Socs3 Modulates Alveolar Bone Loss 2001mentioning

confidence: 99%

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

et al. 2009

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“…To investigate mechanisms or systemic factors that affect osseous repair following bacteria induced bone resorption Table 2 Experimental periodontitis in humanized NOD/SCID gavage model T-cells significantly contribute to periodontal bone loss and tissue inflammation (Teng, et al, 1999) ) (Teng, 2002b) The cytokine, RANKL plays an important role in periodontal bone loss and its production is associated with both Th1 & Th2 responses during periodontal pathogenesis ) (Teng, 2002b) OPG administration significantly abolishes alveolar bone destruction in vivo; IFN-γ treatment increases periodontal bone loss while treatment with IL-10 reduces alveolar bone loss ) (Zhang & Teng, 2006) The antigen CagE found on A. actinomycetemcomitans, which is pro-apoptotic, plays a significant role in periodontal tissue and bone loss (Teng & Hu, 2003) (Teng, 2003) CD11c + dendritic cells can participate in modulating inflammation-induced bone loss by acting as osteoclast precursors (Alnaeeli, Penninger, & Teng, 2006) (Alnaeeli, et al, 2007) …”

Section: Bacterial Virulence Factorsmentioning

confidence: 99%

The use of rodent models to investigate host–bacteria interactions related to periodontal diseases

Graves

Fine

Teng

et al. 2008

J Clinic Periodontology

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344

370

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Even though animal models have limitations they are often superior to in vitro or clinical studies in addressing mechanistic questions and serve as an essential link between hypotheses and human patients. Periodontal disease can be viewed as a process that involves four major stages: bacterial colonization, invasion, induction of a destructive host response in connective tissue and a repair process that reduces the extent of tissue breakdown. Animal studies should be evaluated in terms of their capacity to test specific hypotheses rather than their fidelity to all aspects of periodontal disease initiation and progression. Thus, each of the models described below can be adapted to test discrete components of these four major steps, but not all of them. This review describes five different animal models that are appropriate for examining components of host-bacteria interactions that can lead to breakdown of hard and soft connective tissue or conditions that limit its repair as follows: the mouse calvarial model, murine oral gavage models with or without adoptive transfer of human lymphocytes, rat ligature model and rat Aggregatibacter actinomycetemcomitans feeding model.

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“…Finally, to examine whether the above-described event of cytokine regulation in response to A. actinomycetemcomitans challenge can also be induced by specific microbial Ag in vivo, we employed an A. actinomycetemcomitans-associated CagE homologue (in short, CagE) (48,49) recognized by human CD4 ϩ T cells as a model Ag for testing via an immunization strategy. Based on our previous study, CagE is a critical microbial virulence factor associated with human CD4 ϩ T-cell-mediated destructive immunity for alveolar bone loss and induction of apoptosis of different human cell types in the periodontal tissues (46,(48)(49). Therefore, BALB/c mice were i.p.…”

Section: A Actinomycetemcomitans-reactive Cd4mentioning

confidence: 99%

Gamma Interferon Positively ModulatesActinobacillus actinomycetemcomitans-Specific RANKL⁺CD4⁺Th-Cell-Mediated Alveolar Bone Destruction In Vivo

2005

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Expression cloning of a periodontitis-associated apoptotic effector, cagE homologue, in Actinobacillus actinomycetemcomitans

Cited by 27 publications

References 42 publications

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

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

The use of rodent models to investigate host–bacteria interactions related to periodontal diseases

Gamma Interferon Positively ModulatesActinobacillus actinomycetemcomitans-Specific RANKL⁺CD4⁺Th-Cell-Mediated Alveolar Bone Destruction In Vivo

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Expression cloning of a periodontitis-associated apoptotic effector, cagE homologue, in Actinobacillus actinomycetemcomitans

Cited by 27 publications

References 42 publications

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

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

The use of rodent models to investigate host–bacteria interactions related to periodontal diseases

Gamma Interferon Positively ModulatesActinobacillus actinomycetemcomitans-Specific RANKL+CD4+Th-Cell-Mediated Alveolar Bone Destruction In Vivo

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

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

Gamma Interferon Positively ModulatesActinobacillus actinomycetemcomitans-Specific RANKL⁺CD4⁺Th-Cell-Mediated Alveolar Bone Destruction In Vivo