scholarly journals P124/O27 Osteocyte-derived podoplanin is an important regulator of bone remodelling in the KBxN serum transfer model of rheumatoid arthritis

2019 ◽  
Author(s):  
C Wehmeyer ◽  
AJ Naylor ◽  
K Moeller ◽  
G Poologasundarampillai ◽  
T Pap ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Remodelling ◽  
Transfer Model ◽  
Serum Transfer ◽  
Important Regulator ◽  
Serum Transfer Model

scholarly journals TRANCE/RANKL Knockout Mice Are Protected from Bone Erosion in a Serum Transfer Model of Arthritis

2001 ◽  
Vol 159 (5) ◽  
pp. 1689-1699 ◽  
Author(s):  
Allison R. Pettit ◽  
Hong Ji ◽  
Dietrich von Stechow ◽  
Ralph Müller ◽  
Steven R. Goldring ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Bone Erosion ◽  
Transfer Model ◽  
Serum Transfer ◽  
Serum Transfer Model

scholarly journals Neutrophil-derived leukotriene B4 is required for inflammatory arthritis

2006 ◽  
Vol 203 (4) ◽  
pp. 837-842 ◽  
Author(s):  
Mei Chen ◽  
Bing K. Lam ◽  
Yoshihide Kanaoka ◽  
Peter A. Nigrovic ◽  
Laurent P. Audoly ◽  
...  
Keyword(s):  
Inflammatory Arthritis ◽  
Leukotriene B4 ◽  
Transfer Model ◽  
Effector Functions ◽  
Serum Transfer ◽  
Cellular Source ◽  
Disease Induction ◽  
Deficient Mice ◽  
Arthritis Susceptibility ◽  
Serum Transfer Model

Neutrophils serve as a vanguard of the acute innate immune response to invading pathogens. Neutrophils are also abundant at sites of autoimmune inflammation, such as the rheumatoid joint, although their pathophysiologic role is incompletely defined and relevant effector functions remain obscure. Using genetic and pharmacologic approaches in the K/BxN serum transfer model of arthritis, we find that autoantibody-driven erosive synovitis is critically reliant on the generation of leukotrienes, and more specifically on leukotriene B4 (LTB4), for disease induction as well as perpetuation. Pursuing the cellular source for this mediator, we find via reconstitution experiments that mast cells are a dispensable source of leukotrienes, whereas arthritis susceptibility can be restored to leukotriene-deficient mice by intravenous administration of wild-type neutrophils. These experiments demonstrate a nonredundant role for LTB4 in inflammatory arthritis and define a neutrophil mediator involved in orchestrating the synovial eruption.

scholarly journals Low-Dose Radiotherapy Leads to a Systemic Anti-Inflammatory Shift in the Pre-Clinical K/BxN Serum Transfer Model and Reduces Osteoarthritic Pain in Patients

2022 ◽  
Vol 12 ◽  
Author(s):  
Thomas Weissmann ◽  
Michael Rückert ◽  
Jian-Guo Zhou ◽  
Michaela Seeling ◽  
Sebastian Lettmaier ◽  
...  
Keyword(s):  
Mouse Model ◽  
Molecular Mechanisms ◽  
Low Dose ◽  
Transfer Model ◽  
Clinical Approach ◽  
Analgesic Effects ◽  
Low Dose Radiotherapy ◽  
Serum Transfer ◽  
Highly Effective ◽  
Serum Transfer Model

Osteoarthritis (OA) is the leading degenerative joint disease in the western world and leads, if left untreated, to a progressive deterioration of joint functionality, ultimately reducing quality of life. Recent data has shown, that especially OA of the ankle and foot are among the most frequently affected regions. Current research in OA points towards a complex involvement of various cell and tissue types, often accompanied by inflammation. Low-dose radiotherapy (LDRT) is widely used for the treatment of degenerative and inflammatory diseases. While the reported analgesic effects are well known, the underlying molecular mechanisms are only poorly understood. We therefore correlated a clinical approach, looking at pain reduction in 196 patients treated with LDRT with a pre-clinical approach, utilizing the K/BxN serum transfer mouse model using flow cytometry and multiplex ELISA for analysis. While an improvement of symptoms in the majority of patients was found, patients suffering from symptoms within the tarsi transversa show a significantly lower level of improvement. Further, a significant impact of therapy success was detected depending on whether only one or both feet were affected. Further, patients of younger age showed a significantly better outcome than older ones while needing fewer treatment series. When looking on a cellular level within the mouse model, a systemic alteration of immune cells namely a shift from CD8+ to CD4+ T cells and reduced numbers of DCs was observed. A general reduction of inflammatory cytokines was detected, with significant alterations in IL-4 and IL-17 levels, all of which could potentially be responsible for the highly effective clinical improvement in patients. Taken together our data indicate that LDRT can be regarded as a highly effective treatment option for patients suffering from OA of the foot and ankle, in terms of analgesic effects, especially in younger patients. Furthermore, the observed effects are mediated by an interplay of cellular and soluble immune factors, as observed in the K/BxN serum transfer model. With this interdisciplinary approach we aim to encourage the usage of LDRT as an additive treatment strategy not only as a last resort, but also earlier in the course of disease.

scholarly journals Using the K/BxN mouse model of endogenous, chronic, rheumatoid arthritis for the evaluation of potential immunoglobulin-based therapeutic agents, including IVIg and Fc-μTP-L309C, a recombinant IgG1 Fc hexamer

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Bonnie J. B. Lewis ◽  
Jade Ville ◽  
Megan Blacquiere ◽  
Selena Cen ◽  
Rolf Spirig ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mouse Model ◽  
Autoimmune Diseases ◽  
Chronic Arthritis ◽  
High Dose ◽  
Transfer Model ◽  
Chronic Rheumatoid Arthritis ◽  
Autoimmune Mouse ◽  
Serum Transfer ◽  
Human Igg1

Abstract Background High-dose intravenous immunoglobulin (IVIg), and more recently, subcutaneously-delivered Ig (SCIg), are used to treat a variety of autoimmune diseases; however, there are challenges associated with product production, availability, access and efficacy. These challenges have provided incentives to develop a human recombinant Fc as a more potent alternative to IVIg and SCIg for the treatment of autoimmune diseases. Recently, a recombinant human IgG1 Fc hexamer (Fc-μTP-L309C) was shown to be more efficacious than IVIg in a variety of autoimmune mouse models. We have now examined its efficacy compared to IVIg and SCIg in the K/BxN mouse model of endogenous, chronic rheumatoid arthritis (RA). Result Using the serum-transfer K/BxN model and the endogenous autoimmune model, amelioration of the arthritis was achieved. Effective treatment required high and frequent doses of IVIg, SCIg and Fc-μTP-L309C. However, Fc-μTP-L309C was efficacious at 10-fold lower doses that IVIg/SCIg. Also, arthritis could be prevented when Fc-μTP-L309C was given prior to onset of the arthritis in both the endogenous model and in the serum transfer model. Conclusions Our results show that Fc-μTP-L309C is a powerful treatment for the prevention and amelioration of severe, chronic arthritis in a true autoimmune mouse model of RA. Thus, the K/BxN endogenous arthritis model should be useful for testing potential therapeutics for RA. Our findings provide rationale for further examination of the treatment efficacy of immunoglobulin-based therapeutics in rheumatoid arthritis.

Gene targeting of properdin ameliorates disease development in the K/BxN mouse serum transfer model of arthritis

2008 ◽  
Vol 45 (16) ◽  
pp. 4112
Author(s):  
Yuko Kimura ◽  
Lin Zhou ◽  
David Kim ◽  
Takashi Miwa ◽  
Wen-Chao Song
Keyword(s):  
Gene Targeting ◽  
Mouse Serum ◽  
Transfer Model ◽  
Disease Development ◽  
Serum Transfer ◽  
Serum Transfer Model

scholarly journals Adenovirus-mediated delivery of Sema3A alleviates rheumatoid arthritis in a serum-transfer induced mouse model

Oncotarget ◽  
2017 ◽  
Vol 8 (39) ◽  
pp. 66270-66280 ◽  
Author(s):  
Yue Teng ◽  
Zhanhai Yin ◽  
Jing Li ◽  
Kun Li ◽  
Xu Li ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mouse Model ◽  
Serum Transfer

scholarly journals Hexokinase 2 as a novel selective metabolic target for rheumatoid arthritis

2018 ◽  
Vol 77 (11) ◽  
pp. 1636-1643 ◽  
Author(s):  
Marta F Bustamante ◽  
Patricia G Oliveira ◽  
Ricard Garcia-Carbonell ◽  
Adam P Croft ◽  
Jeff M Smith ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Glucose Metabolism ◽  
Cartilage Damage ◽  
Critical Role ◽  
Lactate Production ◽  
Migration And Invasion ◽  
Synovial Lining ◽  
Serum Transfer ◽  
And Cartilage

ObjectivesRecent studies indicate that glucose metabolism is altered in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS). Hexokinases (HKs) catalyse the first step in glucose metabolism, and HK2 constitutes the principal HK inducible isoform. We hypothesise that HK2 contributes to the synovial lining hypertrophy and plays a critical role in bone and cartilage damage.MethodsHK1 and HK2 expression were determined in RA and osteoarthritis (OA) synovial tissue by immunohistochemistry. RA FLS were transfected with either HK1 or HK2 siRNA, or infected with either adenovirus (ad)-GFP, ad-HK1 or ad-HK2. FLS migration and invasion were assessed. To study the role of HK2 in vivo, 108 particles of ad-HK2 or ad-GFP were injected into the knee of wild-type mice. K/BxN serum transfer arthritis was induced in HK2F/F mice harbouring Col1a1-Cre (HK2Col1), to delete HK2 in non-haematopoietic cells.ResultsHK2 is particular of RA histopathology (9/9 RA; 1/8 OA) and colocalises with FLS markers. Silencing HK2 in RA FLS resulted in a less invasive and migratory phenotype. Consistently, overexpression of HK2 resulted in an increased ability to migrate and invade. It also increased extracellular lactate production. Intra-articular injection of ad-HK2 in normal knees dramatically increased synovial lining thickness, FLS activation and proliferation. HK2 was highly expressed in the synovial lining after K/BxN serum transfer arthritis. HK2Col1 mice significantly showed decreased arthritis severity, bone and cartilage damage.ConclusionHK2 is specifically expressed in RA synovial lining and regulates FLS aggressive functions. HK2 might be an attractive selective metabolic target safer than global glycolysis for RA treatment.

Treating murine inflammatory diseases with an anti-erythrocyte antibody

2019 ◽  
Vol 11 (506) ◽  
pp. eaau8217 ◽  
Author(s):  
Andrew R. Crow ◽  
Rick Kapur ◽  
Sandra Koernig ◽  
Ian K. Campbell ◽  
Chao-Ching Jen ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Inflammatory Cells ◽  
Transfer Model ◽  
Complement Components ◽  
Chemokine Production ◽  
Injury Model ◽  
Serum Transfer ◽  
Autoimmune And Inflammatory Diseases ◽  
Lung Injury Model

Treatment of autoimmune and inflammatory diseases typically involves immune suppression. In an opposite strategy, we show that administration of the highly inflammatory erythrocyte-specific antibody Ter119 into mice remodels the monocyte cellular landscape, leading to resolution of inflammatory disease. Ter119 with intact Fc function was unexpectedly therapeutic in the K/BxN serum transfer model of arthritis. Similarly, it rapidly reversed clinical disease progression in collagen antibody-induced arthritis (CAIA) and collagen-induced arthritis and completely corrected CAIA-induced increase in monocyte Fcγ receptor II/III expression. Ter119 dose-dependently induced plasma chemokines CCL2, CCL5, CXCL9, CXCL10, and CCL11 with corresponding alterations in monocyte percentages in the blood and liver within 24 hours. Ter119 attenuated chemokine production from the synovial fluid and prevented the accumulation of inflammatory cells and complement components in the synovium. Ter119 could also accelerate the resolution of hypothermia and pulmonary edema in an acute lung injury model. We conclude that this inflammatory anti-erythrocyte antibody simultaneously triggers a highly efficient anti-inflammatory effect with broad therapeutic potential.

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