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W.b. Van Den Berg - One of the best experts on this subject based on the ideXlab platform.
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A2.07 Antagonisticregulation of IL-17 and GM-CSF during cell development ex vivo and during Experimental Arthritis
Annals of the Rheumatic Diseases, 2016Co-Authors: Debbie M. Roeleveld, W.b. Van Den Berg, R. Rogier, P.m. Van Der Kraan, Ian P. Wicks, Marije I. KoendersAbstract:Background and objectives GM-CSF is a pro-inflammatory cytokine suggested to be mainly expressed by the Th17 cell subset. Combination blocking of GM-CSF and the key Th17-cytokine IL-17 has shown to be much more effective in reducing Experimental Arthritis compared to single cytokine blocking, revealing a potential connexion between the two cytokines. With this study, we aimed to unravel the interplay between GM-CSF and IL-17 during Th17 differentiation ex vivo and in vivo during Experimental Arthritis. Materials and methods We investigated whether IL-17 and GM-CSF levels were affected in a similar fashion when differentiating naive murine CD4 + T cells ex vivo under conditions suboptimal for Th17 development. Additionally, we determined the effect of incubation with GM-CSF and IL-17 recombinant proteins and neutralising antibodies on expression of both cytokines during ex vivo Th17 differentiation. Finally, we studied the IL-17/GM-CSF interplay in C57Bl6/J mice with mBSA/IL-1β-induced Experimental Arthritis treated with anti-GM-CSF or anti-IL-17 antibodies. Results Interestingly, our ex vivo studies showed increased GM-CSF levels after differentiating naive cells under conditions suboptimal for Th17 development, while IL-17 levels decreased as expected. In line with this ex vivo finding, we observed higher systemic levels of IL-17 and GM-CSF in mice with Experimental Arthritis after GM-CSF and IL-17 neutralisation respectively. Remarkably, no effects of incubation of naive CD4 + T cells with IL-17 or GM-CSF recombinant proteins or neutralising antibodies during T cell differentiation were detected. This indicates that the two cytokines do not directly regulate each other’s expression but require interaction with environmental cells for their suppressive actions. Conclusion These data point towards deviating differentiation conditions and indirect antagonistic regulation of IL-17 and GM-CSF expression by CD4 + T cells, and provides further rationale for a combination blocking strategy of IL-17 and GM-CSF in treatment of Rheumatoid Arthritis.
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FRI0005 Combination Blocking of IL-22 and IL-17 During Experimental Arthritis Potently Reduces TH17-Driven Disease Progression
Annals of the Rheumatic Diseases, 2015Co-Authors: Debbie M. Roeleveld, L. Van Den Bersselaar, W.b. Van Den Berg, R. Rogier, P.m. Van Der Kraan, Birgitte Walgreen, M. M. A. Helsen, Marije I. KoendersAbstract:Background Rheumatoid Arthritis (RA) patients show elevated levels of IL-22 and IL-22-producing T helper cells that correlate to erosive disease, suggesting a role for this cytokine in the pathogenesis of RA. Interestingly, IL-22 is a dual cytokine with pro- and anti-inflammatory properties, and its effects might be regulated by cooperation and crosstalk with IL-17. Objectives The purpose of this study was to elucidate the role of IL-22 in the development of a spontaneous model of Experimental Arthritis by using IL-1Ra knockout mice. Additionally, we aimed to investigate the therapeutic potential of combined IL-22/IL-17 blocking during Experimental Arthritis. Methods IL-1Ra-deficient mice develop spontaneous Arthritis due to excess IL-1 signaling, and we previously demonstrated the importance of IL-17 and Th17 cells in this model 1 . To investigate the role of IL-22 in this Arthritis model, we compared IL-1Ra -/- x IL-22 +/+ mice to IL-1Ra -/- mice lacking IL-22 expression. Paw joint swelling was scored weekly, and mice were sacrificed at the age of fifteen weeks. In addition, arthritic IL-1Ra -/- x IL-22 -/- mice were treated with anti-IL-17 antibodies to determine the therapeutic potency of this combined blocking strategy during Experimental Arthritis. Results IL-1Ra -/- mice that also lack IL-22 showed strongly reduced Arthritis development, reaching a disease incidence of only 54% at the age of 15 weeks compared to 93% in IL-1Ra -/- x IL-22 +/+ mice. In addition, Arthritis severity of the mice that did develop Arthritis was significantly reduced by 30.6% in the absence of IL-22. Interestingly, combined blocking of IL-22 and IL-17 using IL-1Ra -/- x IL-22 -/- mice treated with neutralizing anti-IL-17 antibodies after the onset of Arthritis demonstrated clear additive effects compared to blocking these single cytokines alone, thereby potently reducing progression of this Th17-driven Arthritis model. Conclusions These findings suggest that IL-22 plays an important role both in the initiation and augmentation of Th17-dependent Experimental Arthritis, and that targeting IL-22, especially in combination with IL-17 therefore seems an interesting, potent strategy in RA treatment. References Koenders MI, Devesa I, Marijnissen RJ, Abdollahi-Roodsaz S, Boots AM, Walgreen B, di Padova FE, Nicklin MJ, Joosten LA, van den Berg WB. Interleukin-1 drives pathogenic Th17 cells during spontaneous Arthritis in interleuking-1 receptor antagonist-deficient mice. Arthritis Rheum. 58(11): 3461-70, 2008. Disclosure of Interest None declared
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A novel Saa3-promoter reporter distinguishes inflammatory subtypes in Experimental Arthritis and human synovial fibroblasts
Annals of the rheumatic diseases, 2011Co-Authors: Jeroen Geurts, W.b. Van Den Berg, Onno J. Arntz, Eline A. Vermeij, D. Pohlers, R.w. Kinne, F.a. Van De LooAbstract:OBJECTIVE: To evaluate the applicability of a lentiviral (LV) serum amyloid A3 (Saa3)-promoter luciferase (Luc) reporter for assessing inflammation in Experimental Arthritis, synovial fibroblasts (SF) from osteoArthritis (OA) and rheumatoid Arthritis (RA) patients. METHODS: In mice, synovium was transduced in vivo by cholesterol optimised LV, and two flares of acute joint inflammation were induced by injection of streptococcal cell wall (SCW) material into the knee-joint cavity. The time course of synovial inflammation was assessed using ex vivo luciferase assays, and histology. Uptake of (99m)technetium (Tc) was used to assess oedema. SF (n=12) of RA and OA patients were stratified by hierarchical clustering of whole genome expression profiles. Relative Saa3-promoter responses were determined in cytokine- or toll-like receptor (TLR)-stimulated SF subgroups. RESULTS: In vivo, the Saa3-promoter reporter activity was strongly upregulated at 1 and 2 days after the first and second SCW challenge. The Saa3-promoter activities during acute inflammation correlated with Tc uptake measurements but were more sensitive and able to respond to the ongoing synovitis in the chronic phase of SCW Arthritis. Molecular stratification defined two inflammatory SF subtypes, unrelated to disease classification. Relative Saa3-promoter responses to interleukin 1beta, tumour necrosis factor alpha and TLR4 agonist were significantly increased in OA/RA SF with a high compared to a low inflammatory profile subtype. Serum stimulation of the Saa3-promoter reporter cell-line could distinguish between healthy and RA patients. CONCLUSION: The Saa3-promoter reporter demonstrates a robust and feasible tool for assessing the course and severity of Experimental Arthritis and for distinguishing molecularly distinct inflammatory SF subtypes from a heterogeneous patient population.
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IL-21R deficiency during Experimental Arthritis increases local expression of inflammatory mediators but protects against joint pathology by suppressing Th17 cells
Annals of the Rheumatic Diseases, 2010Co-Authors: Marije I. Koenders, Renoud J. Marijnissen, Cheryl Nickerson-nutter, W.b. Van Den BergAbstract:One of the cytokines that contributes to the formation of Th17 cells is interleukin (IL)21, a pleiotropic cytokine produced by Th17 cells themselves. The purpose of this study was to investigate the effect of IL21R deficiency on joint pathology in relation to Th17 cells during chronic Experimental Arthritis. In IL21R-/- mice, chronic streptococcal cell wall (SCW) Arthritis was induced by intra-articular injections of SCW fragments at days 0, 7, …
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potential new targets in Arthritis therapy interleukin il 17 and its relation to tumour necrosis factor and il 1 in Experimental Arthritis
Annals of the Rheumatic Diseases, 2006Co-Authors: Marije I. Koenders, Leo A B Joosten, W.b. Van Den BergAbstract:Rheumatoid Arthritis (RA) is a systemic autoimmune disease characterised by chronic joint inflammation and destruction. Interleukin (IL)-17 is a T cell cytokine expressed in the synovium and synovial fluid of patients with RA. IL-17 is a potent inducer of various cytokines such as tumour necrosis factor (TNF) and IL-1. IL-17 has been shown to have additive or even synergistic effects with TNF and IL-1 during the induction of cytokine expression and joint damage in vitro and in vivo. TNFalpha and IL-1 are considered powerful targets in the treatment of RA because of their leading role in driving the enhanced production of cytokines, chemokines, and degradative enzymes. Besides anti-TNF and anti-IL-1 therapies, whose clinical efficacy is now established, new targets have been proposed for RA which is not responding to conventional treatments. This paper discusses the role of IL-17 in Experimental Arthritis and its interrelationship with TNF and IL-1, currently the most targeted cytokines in the treatment of RA. IL-17 is involved in both initiation and progression of murine Experimental Arthritis. Studies have shown that IL-17 not only synergises with TNF, but also enhances inflammation and destruction independent of IL-1 and TNF. On the basis of these studies, the authors propose IL-17 as an interesting additional target in the treatment of RA.
Marije I. Koenders - One of the best experts on this subject based on the ideXlab platform.
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Systemic overexpression of interleukin-22 induces the negative immune-regulator SOCS3 and potently reduces Experimental Arthritis in mice.
Rheumatology (Oxford England), 2020Co-Authors: J. Aarts, Debbie M. Roeleveld, Fons A. J. Van De Loo, Birgitte Walgreen, Monique M. Helsen, Elly L. Vitters, Jay K. Kolls, Peter L. E. M. Van Lent, Peter M. Van Der Kraan, Marije I. KoendersAbstract:OBJECTIVE High levels of IL-22 are present in serum and synovial fluid of patients with RA. As both pro- and anti-inflammatory roles for IL-22 have been described in studies using animal models of RA, its exact function in Arthritis remains poorly defined. With this study we aimed to further unravel the mechanism by which IL-22 exerts its effects and to decipher its therapeutic potential by overexpression of IL-22 either locally or systemically during Experimental Arthritis. METHODS CIA was induced in DBA-1 mice by immunization and booster injection with type II collagen (col II). Before Arthritis onset, IL-22 was overexpressed either locally by intra-articular injection or systemically by i.v. injection using an adenoviral vector and clinical Arthritis was scored for a period of 10 days. Subsequently, joints were isolated for histological analysis of Arthritis severity and mRNA and protein expression of various inflammatory mediators was determined in the synovium, spleen and serum. RESULTS Local IL-22 overexpression did not alter Arthritis pathology, whereas systemic overexpression of IL-22 potently reduced disease incidence, severity and pathology during CIA. Mice systemically overexpressing IL-22 showed strongly reduced serum cytokine levels of TNF-α and macrophage inflammatory protein 1α that correlated significantly with the enhanced expression of the negative immune regulator SOCS3 in the spleen. CONCLUSION With this study, we revealed clear anti-inflammatory effects of systemic IL-22 overexpression during CIA. Additionally, we are the first to show that the protective effect of systemic IL-22 during Experimental Arthritis is likely orchestrated via upregulation of the negative regulator SOCS3.
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A2.07 Antagonisticregulation of IL-17 and GM-CSF during cell development ex vivo and during Experimental Arthritis
Annals of the Rheumatic Diseases, 2016Co-Authors: Debbie M. Roeleveld, W.b. Van Den Berg, R. Rogier, P.m. Van Der Kraan, Ian P. Wicks, Marije I. KoendersAbstract:Background and objectives GM-CSF is a pro-inflammatory cytokine suggested to be mainly expressed by the Th17 cell subset. Combination blocking of GM-CSF and the key Th17-cytokine IL-17 has shown to be much more effective in reducing Experimental Arthritis compared to single cytokine blocking, revealing a potential connexion between the two cytokines. With this study, we aimed to unravel the interplay between GM-CSF and IL-17 during Th17 differentiation ex vivo and in vivo during Experimental Arthritis. Materials and methods We investigated whether IL-17 and GM-CSF levels were affected in a similar fashion when differentiating naive murine CD4 + T cells ex vivo under conditions suboptimal for Th17 development. Additionally, we determined the effect of incubation with GM-CSF and IL-17 recombinant proteins and neutralising antibodies on expression of both cytokines during ex vivo Th17 differentiation. Finally, we studied the IL-17/GM-CSF interplay in C57Bl6/J mice with mBSA/IL-1β-induced Experimental Arthritis treated with anti-GM-CSF or anti-IL-17 antibodies. Results Interestingly, our ex vivo studies showed increased GM-CSF levels after differentiating naive cells under conditions suboptimal for Th17 development, while IL-17 levels decreased as expected. In line with this ex vivo finding, we observed higher systemic levels of IL-17 and GM-CSF in mice with Experimental Arthritis after GM-CSF and IL-17 neutralisation respectively. Remarkably, no effects of incubation of naive CD4 + T cells with IL-17 or GM-CSF recombinant proteins or neutralising antibodies during T cell differentiation were detected. This indicates that the two cytokines do not directly regulate each other’s expression but require interaction with environmental cells for their suppressive actions. Conclusion These data point towards deviating differentiation conditions and indirect antagonistic regulation of IL-17 and GM-CSF expression by CD4 + T cells, and provides further rationale for a combination blocking strategy of IL-17 and GM-CSF in treatment of Rheumatoid Arthritis.
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Monitoring Therapy Response of Experimental Arthritis with Radiolabeled Tracers Targeting Fibroblasts, Macrophages, or Integrin αvβ3
Journal of nuclear medicine : official publication Society of Nuclear Medicine, 2015Co-Authors: Samantha Y. A. Terry, Marije I. Koenders, Gerben M. Franssen, Tapan K. Nayak, Anne Freimoser-grundschober, Christian Klein, Wim J.g. Oyen, Otto C. Boerman, Peter LavermanAbstract:Rheumatoid Arthritis is an autoimmune disease resulting in chronic synovial inflammation. Molecular imaging could be used to monitor therapy response, thus enabling tailored therapy regimens and enhancing therapeutic outcome. Here, we hypothesized that response to etanercept could be monitored by radionuclide imaging in arthritic mice. We tested 3 different targets, namely fibroblast activation protein (FAP), macrophages, and integrin αvβ3. Methods: Male DBA/1J mice with collagen-induced Arthritis were treated with etanercept. SPECT/CT scans were acquired at 1, 24, and 48 h after injection of 111In-RGD2 (integrin αvβ3), 111In-anti-F4/80-A3-1 (antimurine macrophage antibody), or 111In-28H1 (anti-FAP antibody), respectively, with nonspecific controls included. Mice were dissected after the last scan, and scans were analyzed quantitatively and were correlated with macroscopic scoring. Results: Experimental Arthritis was imaged with 111In-28H1 (anti-FAP), 111In-anti-F4/80-A3-1, and 111In-RGD2. Tracer uptake in joints correlated with Arthritis score. Treatment decreased joint uptake of tracers from 23 ± 15, 8 ± 4, and 2 ± 1 percentage injected dose per gram (%ID/g) to 11 ± 11 (P 25), 111In-anti-F4/80-A3-1 (10.4 ± 4), and 111In-RGD2 (7.2 ± 1) than for control 111In-DP47GS (0.7 ± 0.5; P = 0.002), 111In-rat IgG2b (0.5 ± 0.2; P = 0.002), or coinjection of excess RGD2 (3.5), indicating specific uptake of all tracers in arthritic joints. Conclusion:111In-28H1, 111In-anti-F4/80-A3-1, and 111In-RGD2 can be used to specifically monitor the response to therapy in Experimental Arthritis at the molecular level. Further studies, however, still need to be performed.
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FRI0005 Combination Blocking of IL-22 and IL-17 During Experimental Arthritis Potently Reduces TH17-Driven Disease Progression
Annals of the Rheumatic Diseases, 2015Co-Authors: Debbie M. Roeleveld, L. Van Den Bersselaar, W.b. Van Den Berg, R. Rogier, P.m. Van Der Kraan, Birgitte Walgreen, M. M. A. Helsen, Marije I. KoendersAbstract:Background Rheumatoid Arthritis (RA) patients show elevated levels of IL-22 and IL-22-producing T helper cells that correlate to erosive disease, suggesting a role for this cytokine in the pathogenesis of RA. Interestingly, IL-22 is a dual cytokine with pro- and anti-inflammatory properties, and its effects might be regulated by cooperation and crosstalk with IL-17. Objectives The purpose of this study was to elucidate the role of IL-22 in the development of a spontaneous model of Experimental Arthritis by using IL-1Ra knockout mice. Additionally, we aimed to investigate the therapeutic potential of combined IL-22/IL-17 blocking during Experimental Arthritis. Methods IL-1Ra-deficient mice develop spontaneous Arthritis due to excess IL-1 signaling, and we previously demonstrated the importance of IL-17 and Th17 cells in this model 1 . To investigate the role of IL-22 in this Arthritis model, we compared IL-1Ra -/- x IL-22 +/+ mice to IL-1Ra -/- mice lacking IL-22 expression. Paw joint swelling was scored weekly, and mice were sacrificed at the age of fifteen weeks. In addition, arthritic IL-1Ra -/- x IL-22 -/- mice were treated with anti-IL-17 antibodies to determine the therapeutic potency of this combined blocking strategy during Experimental Arthritis. Results IL-1Ra -/- mice that also lack IL-22 showed strongly reduced Arthritis development, reaching a disease incidence of only 54% at the age of 15 weeks compared to 93% in IL-1Ra -/- x IL-22 +/+ mice. In addition, Arthritis severity of the mice that did develop Arthritis was significantly reduced by 30.6% in the absence of IL-22. Interestingly, combined blocking of IL-22 and IL-17 using IL-1Ra -/- x IL-22 -/- mice treated with neutralizing anti-IL-17 antibodies after the onset of Arthritis demonstrated clear additive effects compared to blocking these single cytokines alone, thereby potently reducing progression of this Th17-driven Arthritis model. Conclusions These findings suggest that IL-22 plays an important role both in the initiation and augmentation of Th17-dependent Experimental Arthritis, and that targeting IL-22, especially in combination with IL-17 therefore seems an interesting, potent strategy in RA treatment. References Koenders MI, Devesa I, Marijnissen RJ, Abdollahi-Roodsaz S, Boots AM, Walgreen B, di Padova FE, Nicklin MJ, Joosten LA, van den Berg WB. Interleukin-1 drives pathogenic Th17 cells during spontaneous Arthritis in interleuking-1 receptor antagonist-deficient mice. Arthritis Rheum. 58(11): 3461-70, 2008. Disclosure of Interest None declared
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A1.22 IL-22 Drives the initiation and augmentation of TH17-dependent Experimental Arthritis
Annals of the Rheumatic Diseases, 2014Co-Authors: Debbie M. Roeleveld, Wim B. Van Den Berg, Renoud J. Marijnissen, Marije I. KoendersAbstract:Background Rheumatoid Arthritis (RA) is a chronic, inflammatory autoimmune disease that leads to progressive destruction of cartilage and bone. IL-22 and IL-22-producing T helper cells are elevated in RA patients, suggesting a role for this cytokine in the pathogenesis of this disease. Interestingly, IL-22 is a dual cytokine with both proinflammatory and anti-inflammatory properties, and therefore its exact role in RA pathology requires further investigation. Objectives The aim of this study was to explore the role of IL-22 in the initiation and severity of a spontaneous model of Experimental Arthritis by using gene knockout mice and neutralizing antibodies for IL-22. In addition, we aimed to determine the influence of IL-22 on T cell subsets and cytokines in our mouse model. Methods IL-1Ra-deficient mice develop spontaneous Arthritis due to excess IL-1 signaling, and we previously demonstrated the importance of IL-17 and Th17 cells in this model (Koenders, Arthritis Rheum 2008). To investigate the role of IL-22 in this Th17-dependent Arthritis model, we compared IL-1Ra–/– x IL-22+/+ mice to mice lacking both IL-1Ra and IL-22. Paw joint swelling was scored weekly, and mice were sacrificed at the age of fifteen weeks. In addition, IL-1Ra-deficient mice were treated for 4 weeks with anti-IL-22 neutralizing antibodies administered after onset of Arthritis to inhibit disease progression. Results IL-1Ra–/– mice also deficient for IL-22 showed reduced incidence of Arthritis, as well as reduced joint swelling and bone erosion. In line with the suppressed Arthritis, the proinflammatory Th1 and Th17 cell numbers were decreased in spleens of mice lacking IL-22. Interestingly, also the levels of Treg cells were suppressed in the double knockout mice. Furthermore, IL-1Ra-deficient mice treated with anti-IL-22 antibodies after the clinical onset of Arthritis showed reduced progression on inflammation and significant inhibition on bone erosion. This indicates that not only the onset but also the progression of Arthritis is dependent on IL-22. Interestingly, reduced IL-17 serum levels were found after IL-22 blocking, suggesting a not previously observed feedback loop of IL-22 on Th17 cells. Conclusions These findings suggest that the Th17 cytokine IL-22 plays an important role both in initiation and augmentation of Experimental Arthritis, and might therefore be an interesting new target in RA treatment. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.3528
Mark Bartold - One of the best experts on this subject based on the ideXlab platform.
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porphyromonas gingivalis peptidylarginine deiminase a key contributor in the pathogenesis of Experimental periodontal disease and Experimental Arthritis
PLOS ONE, 2014Co-Authors: N J Gully, Richard Bright, Victor Marino, Ceilidh Marchant, Melissa Cantley, D R Haynes, Catherine A Butler, Stuart G Dashper, Eric C Reynolds, Mark BartoldAbstract:Objectives To investigate the suggested role of Porphyromonas gingivalis peptidylarginine deiminase (PAD) in the relationship between the aetiology of periodontal disease and Experimentally induced Arthritis and the possible association between these two conditions. Methods A genetically modified PAD-deficient strain of P. gingivalis W50 was produced. The effect of this strain, compared to the wild type, in an established murine model for Experimental periodontitis and Experimental Arthritis was assessed. Experimental periodontitis was induced following oral inoculation with the PAD-deficient and wild type strains of P. gingivalis. Experimental Arthritis was induced via the collagen antibody induction process and was monitored by assessment of paw swelling and micro-CT analysis of the radio-carpal joints. Experimental periodontitis was monitored by micro CT scans of the mandible and histological assessment of the periodontal tissues around the mandibular molars. Serum levels of anti-citrullinated protein antibodies (ACPA) and P. gingivalis were assessed by ELISA. Results The development of Experimental periodontitis was significantly reduced in the presence of the PAD-deficient P. gingivalis strain. When Experimental Arthritis was induced in the presence of the PAD-deficient strain there was less paw swelling, less erosive bone damage to the joints and reduced serum ACPA levels when compared to the wild type P. gingivalis inoculated group. Conclusion This study has demonstrated that a PAD-deficient strain of P. gingivalis was associated with significantly reduced periodontal inflammation. In addition the extent of Experimental Arthritis was significantly reduced in animals exposed to prior induction of periodontal disease through oral inoculation of the PAD-deficient strain versus the wild type. This adds further evidence to the potential role for P. gingivalis and its PAD in the pathogenesis of periodontitis and exacerbation of Arthritis. Further studies are now needed to elucidate the mechanisms which drive these processes.
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pre existing periodontitis exacerbates Experimental Arthritis in a mouse model
Journal of Clinical Periodontology, 2011Co-Authors: Melissa D Cantley, Victor Marino, D R Haynes, Mark BartoldAbstract:Cantley MD, Haynes DR, Marino V, Bartold PM: Pre-existing periodontitis exacerbates Experimental Arthritis in a mouse model. J Clin Periodontol 2011; doi: 10.1111/j.1600-051X.2011.01714.x. Abstract Aims: Previous studies have shown a higher incidence of alveolar bone loss in patients with rheumatoid Arthritis (RA) and that patients with periodontitis are at a greater risk of developing RA. The aim of this study was to develop an animal model to assess the relationship between pre-existing periodontitis and Experimental Arthritis (EA). Methods: Periodontitis was first induced in mice by oral gavage with Porphyromonas gingivalis followed by EA using the collagen antibody-induced Arthritis model. These animals were compared with animals with periodontitis alone, EA alone and no disease (controls). Visual changes in paw swelling were assessed to determine clinical development of EA. Alveolar bone and joint changes were assessed using micro-CT, histological analyses and immunohistochemistry. Serum levels of C-reactive protein were used to monitor systemic inflammation. Results: Mice with pre-existing periodontitis developed more severe Arthritis, which developed at a faster rate. Mice with periodontitis only also showed evidence of loss of bone within the radiocarpal joint. There was also evidence of alveolar bone loss in mice with EA alone. Conclusions: The results of this study indicate that pre-existing periodontitis exacerbated Experimental Arthritis in a mouse model.
Victor Marino - One of the best experts on this subject based on the ideXlab platform.
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porphyromonas gingivalis peptidylarginine deiminase a key contributor in the pathogenesis of Experimental periodontal disease and Experimental Arthritis
PLOS ONE, 2014Co-Authors: N J Gully, Richard Bright, Victor Marino, Ceilidh Marchant, Melissa Cantley, D R Haynes, Catherine A Butler, Stuart G Dashper, Eric C Reynolds, Mark BartoldAbstract:Objectives To investigate the suggested role of Porphyromonas gingivalis peptidylarginine deiminase (PAD) in the relationship between the aetiology of periodontal disease and Experimentally induced Arthritis and the possible association between these two conditions. Methods A genetically modified PAD-deficient strain of P. gingivalis W50 was produced. The effect of this strain, compared to the wild type, in an established murine model for Experimental periodontitis and Experimental Arthritis was assessed. Experimental periodontitis was induced following oral inoculation with the PAD-deficient and wild type strains of P. gingivalis. Experimental Arthritis was induced via the collagen antibody induction process and was monitored by assessment of paw swelling and micro-CT analysis of the radio-carpal joints. Experimental periodontitis was monitored by micro CT scans of the mandible and histological assessment of the periodontal tissues around the mandibular molars. Serum levels of anti-citrullinated protein antibodies (ACPA) and P. gingivalis were assessed by ELISA. Results The development of Experimental periodontitis was significantly reduced in the presence of the PAD-deficient P. gingivalis strain. When Experimental Arthritis was induced in the presence of the PAD-deficient strain there was less paw swelling, less erosive bone damage to the joints and reduced serum ACPA levels when compared to the wild type P. gingivalis inoculated group. Conclusion This study has demonstrated that a PAD-deficient strain of P. gingivalis was associated with significantly reduced periodontal inflammation. In addition the extent of Experimental Arthritis was significantly reduced in animals exposed to prior induction of periodontal disease through oral inoculation of the PAD-deficient strain versus the wild type. This adds further evidence to the potential role for P. gingivalis and its PAD in the pathogenesis of periodontitis and exacerbation of Arthritis. Further studies are now needed to elucidate the mechanisms which drive these processes.
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pre existing periodontitis exacerbates Experimental Arthritis in a mouse model
Journal of Clinical Periodontology, 2011Co-Authors: Melissa D Cantley, Victor Marino, D R Haynes, Mark BartoldAbstract:Cantley MD, Haynes DR, Marino V, Bartold PM: Pre-existing periodontitis exacerbates Experimental Arthritis in a mouse model. J Clin Periodontol 2011; doi: 10.1111/j.1600-051X.2011.01714.x. Abstract Aims: Previous studies have shown a higher incidence of alveolar bone loss in patients with rheumatoid Arthritis (RA) and that patients with periodontitis are at a greater risk of developing RA. The aim of this study was to develop an animal model to assess the relationship between pre-existing periodontitis and Experimental Arthritis (EA). Methods: Periodontitis was first induced in mice by oral gavage with Porphyromonas gingivalis followed by EA using the collagen antibody-induced Arthritis model. These animals were compared with animals with periodontitis alone, EA alone and no disease (controls). Visual changes in paw swelling were assessed to determine clinical development of EA. Alveolar bone and joint changes were assessed using micro-CT, histological analyses and immunohistochemistry. Serum levels of C-reactive protein were used to monitor systemic inflammation. Results: Mice with pre-existing periodontitis developed more severe Arthritis, which developed at a faster rate. Mice with periodontitis only also showed evidence of loss of bone within the radiocarpal joint. There was also evidence of alveolar bone loss in mice with EA alone. Conclusions: The results of this study indicate that pre-existing periodontitis exacerbated Experimental Arthritis in a mouse model.
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Pre‐existing periodontitis exacerbates Experimental Arthritis in a mouse model
Journal of clinical periodontology, 2011Co-Authors: Melissa Cantley, Victor Marino, David R. Haynes, P. Mark BartoldAbstract:Cantley MD, Haynes DR, Marino V, Bartold PM: Pre-existing periodontitis exacerbates Experimental Arthritis in a mouse model. J Clin Periodontol 2011; doi: 10.1111/j.1600-051X.2011.01714.x. Abstract Aims: Previous studies have shown a higher incidence of alveolar bone loss in patients with rheumatoid Arthritis (RA) and that patients with periodontitis are at a greater risk of developing RA. The aim of this study was to develop an animal model to assess the relationship between pre-existing periodontitis and Experimental Arthritis (EA). Methods: Periodontitis was first induced in mice by oral gavage with Porphyromonas gingivalis followed by EA using the collagen antibody-induced Arthritis model. These animals were compared with animals with periodontitis alone, EA alone and no disease (controls). Visual changes in paw swelling were assessed to determine clinical development of EA. Alveolar bone and joint changes were assessed using micro-CT, histological analyses and immunohistochemistry. Serum levels of C-reactive protein were used to monitor systemic inflammation. Results: Mice with pre-existing periodontitis developed more severe Arthritis, which developed at a faster rate. Mice with periodontitis only also showed evidence of loss of bone within the radiocarpal joint. There was also evidence of alveolar bone loss in mice with EA alone. Conclusions: The results of this study indicate that pre-existing periodontitis exacerbated Experimental Arthritis in a mouse model.
Melissa Cantley - One of the best experts on this subject based on the ideXlab platform.
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porphyromonas gingivalis peptidylarginine deiminase a key contributor in the pathogenesis of Experimental periodontal disease and Experimental Arthritis
PLOS ONE, 2014Co-Authors: N J Gully, Richard Bright, Victor Marino, Ceilidh Marchant, Melissa Cantley, D R Haynes, Catherine A Butler, Stuart G Dashper, Eric C Reynolds, Mark BartoldAbstract:Objectives To investigate the suggested role of Porphyromonas gingivalis peptidylarginine deiminase (PAD) in the relationship between the aetiology of periodontal disease and Experimentally induced Arthritis and the possible association between these two conditions. Methods A genetically modified PAD-deficient strain of P. gingivalis W50 was produced. The effect of this strain, compared to the wild type, in an established murine model for Experimental periodontitis and Experimental Arthritis was assessed. Experimental periodontitis was induced following oral inoculation with the PAD-deficient and wild type strains of P. gingivalis. Experimental Arthritis was induced via the collagen antibody induction process and was monitored by assessment of paw swelling and micro-CT analysis of the radio-carpal joints. Experimental periodontitis was monitored by micro CT scans of the mandible and histological assessment of the periodontal tissues around the mandibular molars. Serum levels of anti-citrullinated protein antibodies (ACPA) and P. gingivalis were assessed by ELISA. Results The development of Experimental periodontitis was significantly reduced in the presence of the PAD-deficient P. gingivalis strain. When Experimental Arthritis was induced in the presence of the PAD-deficient strain there was less paw swelling, less erosive bone damage to the joints and reduced serum ACPA levels when compared to the wild type P. gingivalis inoculated group. Conclusion This study has demonstrated that a PAD-deficient strain of P. gingivalis was associated with significantly reduced periodontal inflammation. In addition the extent of Experimental Arthritis was significantly reduced in animals exposed to prior induction of periodontal disease through oral inoculation of the PAD-deficient strain versus the wild type. This adds further evidence to the potential role for P. gingivalis and its PAD in the pathogenesis of periodontitis and exacerbation of Arthritis. Further studies are now needed to elucidate the mechanisms which drive these processes.
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Pre‐existing periodontitis exacerbates Experimental Arthritis in a mouse model
Journal of clinical periodontology, 2011Co-Authors: Melissa Cantley, Victor Marino, David R. Haynes, P. Mark BartoldAbstract:Cantley MD, Haynes DR, Marino V, Bartold PM: Pre-existing periodontitis exacerbates Experimental Arthritis in a mouse model. J Clin Periodontol 2011; doi: 10.1111/j.1600-051X.2011.01714.x. Abstract Aims: Previous studies have shown a higher incidence of alveolar bone loss in patients with rheumatoid Arthritis (RA) and that patients with periodontitis are at a greater risk of developing RA. The aim of this study was to develop an animal model to assess the relationship between pre-existing periodontitis and Experimental Arthritis (EA). Methods: Periodontitis was first induced in mice by oral gavage with Porphyromonas gingivalis followed by EA using the collagen antibody-induced Arthritis model. These animals were compared with animals with periodontitis alone, EA alone and no disease (controls). Visual changes in paw swelling were assessed to determine clinical development of EA. Alveolar bone and joint changes were assessed using micro-CT, histological analyses and immunohistochemistry. Serum levels of C-reactive protein were used to monitor systemic inflammation. Results: Mice with pre-existing periodontitis developed more severe Arthritis, which developed at a faster rate. Mice with periodontitis only also showed evidence of loss of bone within the radiocarpal joint. There was also evidence of alveolar bone loss in mice with EA alone. Conclusions: The results of this study indicate that pre-existing periodontitis exacerbated Experimental Arthritis in a mouse model.
