hTNFtg Mice Research Articles

Characterization and quantification of angiogenesis in rheumatoid arthritis in a mouse model using μCT

BackgroundAngiogenesis is an important pathophysiological process of chronic inflammation, especially in inflammatory arthritis. Quantitative measurement of changes in vascularization may improve the diagnosis and monitoring of arthritis. The aim of this work is the development of a 3D imaging and analysis framework for quantification of vascularization in experimental arthritis.MethodsHigh-resolution micro-computed tomography (μCT) was used to scan knee joints of arthritic human tumor necrosis factor transgenic (hTNFtg) mice and non-arthritic wild-type controls previously perfused with lead-containing contrast agent Microfil MV-122. Vessel segmentation was performed by combination of intensity-based (local adaptive thresholding) and form-based (multi-scale method) segmentation techniques. Four anatomically defined concentric spherical shells centered in the knee joint were used as analysis volumes of interest. Vessel density, density distribution as well as vessel thickness, surface, spacing and number were measured. Simulated digital vessel tree models were used for validation of the algorithms.ResultsHigh-resolution μCT allows the quantitative assessment of the vascular tree in the knee joint during arthritis. Segmentation and analysis were highly automated but occasionally required manual corrections of the vessel segmentation close to the bone surfaces. Vascularization was significantly increased in arthritic hTNFtg mice compared to wild type controls. Precision errors for the morphologic parameters were smaller than 3% and 6% for intra- and interoperator analysis, respectively. Accuracy errors for vessel thickness were around 20% for vessels larger than twice the resolution of the scanner.ConclusionsArthritis-induced changes of the vascular tree, including detailed and quantitative description of the number of vessel branches, length of vessel segments and the bifurcation angle, can be detected by contrast-enhanced high-resolution μCT.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2474-15-298) contains supplementary material, which is available to authorized users.

FHL2 regulates the resolution of tissue damage in chronic inflammatory arthritis

ObjectiveWe analysed the role of the adaptor molecule four-and-a-half Lin11, Isl-1 & Mec-3 (LIM) domain protein 2 (FHL2) in the activation of fibroblast-like synoviocytes in human rheumatoid arthritis (RA) and...

Blockade of IL-36 receptor signaling does not prevent from TNF-induced arthritis.

IntroductionInterleukin (IL)-36α is a newly described member of the IL-1 cytokine family with a known inflammatory and pathogenic function in psoriasis. Recently, we could demonstrate that the receptor (IL-36R), its ligand IL-36α and its antagonist IL-36Ra are expressed in synovial tissue of arthritis patients. Furthermore, IL-36α induces MAP-kinase and NFκB signaling in human synovial fibroblasts with subsequent expression and secretion of pro-inflammatory cytokines.MethodsTo understand the pathomechanism of IL-36 dependent inflammation, we investigated the biological impact of IL-36α signaling in the hTNFtg mouse. Also the impact on osteoclastogenesis by IL-36α was tested in murine and human osteoclast assays.ResultsDiseased mice showed an increased expression of IL-36R and IL-36α in inflamed knee joints compared to wildtype controls. However, preventively treating mice with an IL-36R blocking antibody led to no changes in clinical onset and pattern of disease. Furthermore, blockade of IL-36 signaling did not change histological signs of TNF-induced arthritis. Additionally, no alteration on bone homeostasis was observed in ex vivo murine and human osteoclast differentiation assays.ConclusionThus we conclude that IL-36α does not affect the development of inflammatory arthritis.

OP0125 The Role of Microrna-146 in Inflammatory Arthritis

BackgroundMicroRNA (MiR-) 146a is a key regulator of the innate immune response and has also been shown to suppress cancer development in myeloid cells. Elevated expression of miR-146a has been...

SAT0563 Integrin α11β1 is Induced in Synovial Fibroblasts of Arthritic Htnftg Mice

BackgroundCell-matrix interactions of synovial fibroblasts (SF) with cartilage components via β1 integrins are of importance not only for cartilage degradation, but also for the persistence of synovial inflammation during rheumatoid...

SAT0549 Osteoclast Precursors Are Reugulated by Proinflammatory Cytokines and Arise before Clinical Onset of Arthritis

BackgroundBone erosions and systemic bone loss in rheumatoid arthritis patients results from an increased activity of osteoclast, which are derived from precursor cells of the myeloid lineage. Although there is...

A1.23 Lasp-1 deficiency modifies synovial fibroblast migration and cartilage destruction in a model of HTNF alpha mediated arthritis

Background and ObjectivesLasp-1 is an important actin-crosslinking protein. It’s localises at focal adhesions, along stress fibres and leading edges and is involved in cellular migration and metastatic dissemination of different...

A1.81 Mincle is not essential in T-cell independent arthritis models

BackgroundC-type lectin receptor Mincle (also known as Clecsf9, Clec4e) is expressed by monocytes, macrophages and dendritic cells and involved in immune response to various infections. Recent reports showed elevated levels...

A8.37 The role of microRNA-146a in inflammatory Arthritis

BackgroundMicroRNA (MiR)146a is a key regulator of the innate immune response and has also been shown to suppress cancer development in myeloid cells. Elevated expression of miR-146a has been detected...

A6.4 Induction of TH2 cells and eosinophil by infection with nippostrongylus brasiliensis protects against rheumatoid arthritis

Background and ObjectiveInfection with helminth triggers strong Th2 immune response, which modulates the development of systemic autoimmune diseases. The aim of this study was to investigate whether infection with Nippostrongylus...

A1.82 Limited role of microrna 155 innate immunity dependent arthritis

BackgroundMicroRNA 155 (miR155) has been demonstrated to be essential for the development of collagen induced arthritis by controlling the generation of autoreactive T and B cells. However, the contribution of...

Loss of phosphatase and tensin homolog (PTEN) in myeloid cells controls inflammatory bone destruction by regulating the osteoclastogenic potential of myeloid cells

ObjectiveLocal bone destruction in rheumatic diseases, which often leads to disability and severely reduced quality of life, is almost exclusively mediated by osteoclasts. Therefore, it is important to understand pathways...

THU0114 The Loss of S100A4 Prevents Joint Destruction and Systemic Bone Loss in hTNFtg Mouse Model

BackgroundOur previous studies demonstrated increased levels of S100A4 protein in sera, synovial fluid and synovial membrane of patients with rheumatoid arthritis (RA) compared to osteoarthritis. S100A4 regulates apoptosis and induces...

SAT0050 A novel function of junctional adhesion molecule-C in regulation of trans-endothelial migration of murine synovial fibroblasts

BackgroundRecent studies demonstrated the potential of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) to emigrate from affected joints and migrate via the bloodstream toward distant healthy cartilage in the SCID mouse model...

SAT0077 Sumo-2/3 regulates apoptosis and MMP expression in rheumatoid arthritis synovial fibroblasts

BackgroundPosttranslational modification of SUMO to target proteins regulates diverse cellular functions, including transcription, nuclear translocation, stress response and protein stability. Previously, we showed that the increased expression of SUMO-1 in...

AB0174 Muscle wasting in HTNFTG mice; an animal model for rheumatoid arthritis; due to increased cathepsin l expression

ObjectivesTo investigate the impact of systemic inflammation on skeletal muscles in human tumor necrosis factor transgenic (hTNFtg) animals.MethodsWe isolated triceps surae, as well as rectus abdominis muscles from hTNFtg animals...

FRI0033 The inhibitory effects of the yersinia outer protein m (YOPM) on osteoclastogenesis and bone destruction

BackgroundThe severe bone destruction during rheumatoid arthritis (RA) is mainly mediated by osteoclasts and thus, reducing osteoclast number is a keystep in ameliorating the outcome of the disease. Yersinia strains...

THU0117 Loss of PTEN in Myeloid Cells Controls Inflammatory Bone Destruction by Regulating the Osteoclastogenic Potential of Myeloid Cells

BackgroundLocal bone destruction in rheumatoid arthritis, psoriasisarthritis or ankylosing spondylitis is a serious health burden and the major cause of disability and severely reduced quality of life in these diseases....

SAT0057 Functional impairment in an animal model for rheumatoid arthritis assessed as changes in gait is due to joint destruction but not synovial inflammation per SE

ObjectivesTo investigate the individual impact of synovial inflammation, subchondral bone erosion or cartilage damage on functional impairment in an animal model of Rheumatoid Arthritis (RA).MethodsWe analysed gait profiles in human...

THU0018 Sumo specific proteases 5 and 7 contribute to the inbalanced sumoylation level of rheumatoid athritis synovial fibroblasts

BackgroundIt has been shown previousely that posttranslational protein modification through SUMOylation is enhanced in rheumatoid athritis synovial fibroblasts (RASF) compared to osteoathritis synovial fibroblasts (OASF) and that higher levels of...