A5089500564- Bone Metabolism and Diseases
- Rheumatoid Arthritis Research and Therapies
- Bone health and treatments
- Vasculitis and related conditions
- Bone health and osteoporosis research
- Connective tissue disorders research
- Eosinophilic Disorders and Syndromes
- Bone and Joint Diseases
- Systemic Sclerosis and Related Diseases
- Osteoarthritis Treatment and Mechanisms
- Alkaline Phosphatase Research Studies
- Cytokine Signaling Pathways and Interactions
- Urticaria and Related Conditions
- Hip and Femur Fractures
- Parathyroid Disorders and Treatments
- Trace Elements in Health
- Iron Metabolism and Disorders
- Hemoglobinopathies and Related Disorders
- NF-κB Signaling Pathways
- Vitamin D Research Studies
- Inflammatory mediators and NSAID effects
- Spondyloarthritis Studies and Treatments
- Cell Adhesion Molecules Research
- Immune Response and Inflammation
- Mast cells and histamine
Ludwig Boltzmann Institute of Osteology
2016-2025
Hanusch Hospital
2016-2025
Ludwig Boltzmann Institute for Digital Health and Prevention
2004-2024
Allgemeine Unfallversicherungsanstalt
2012-2024
Unfallkrankenhaus Meidling
2015-2021
Western University
2021
Applied Optimization (United States)
2020
Ordensklinikum Linz Barmherzige Schwestern
2020
Friedrich-Alexander-Universität Erlangen-Nürnberg
2007-2019
Universitätsklinikum Erlangen
2007-2019
Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis is a severe condition encompassing two major syndromes: granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) and microscopic polyangiitis. Its cause unknown, there debate about whether it single disease entity what role ANCA plays in its pathogenesis. We investigated genetic basis.
The transforming growth factor-β (TGF-β) signalling pathway is a key mediator of fibroblast activation that drives the aberrant synthesis extracellular matrix in fibrotic diseases. Here we demonstrate novel link between and canonical Wnt pathway. TGF-β stimulates p38-dependent manner by decreasing expression antagonist Dickkopf-1. Tissue samples from human diseases show enhanced proteins decreased Activation fibroblasts vitro induces fibrosis vivo. Transgenic overexpression Dickkopf-1...
Imatinib mesylate is a clinically well-tolerated small molecule inhibitor that exerts selective, dual inhibition of the transforming growth factor beta (TGFbeta) and platelet-derived (PDGF) pathways. This study was undertaken to test potential use imatinib as an antifibrotic drug for treatment dermal fibrosis in systemic sclerosis (SSc).The expression extracellular matrix (ECM) proteins SSc normal fibroblasts analyzed by real-time polymerase chain reaction, Western blot, Sircol collagen...
Abstract Objective To investigate whether Treg cells can suppress osteoclast differentiation, and to define a new potential link between the immune system skeleton. Methods Regulatory CD4+,CD25+,Foxp3+ T were isolated purified from spleen cocultured with CD11b+ precursor bone marrow. Osteoclastogenesis erosion assessed by tartrate‐resistant acid phosphatase staining pit resorption assay, respectively. In addition, Transwell experiments cytokine‐blocking performed mechanisms of interaction...
Abstract Objective Osteocytes are considered to be sensors of bone damage and regulators mass by specifically expressing sclerostin, an inhibitor formation. The contribution osteocytes in regulating local remodeling arthritis is unknown. aim this study was investigate the role as contributors ankylosing spondylitis (AS). Methods Sclerostin expression osteocyte death were assessed immunohistochemistry joints derived from patients with AS, rheumatoid (RA), osteoarthritis (OA), well control...
To evaluate if type 2 diabetes is an independent risk predictor for severe osteoarthritis (OA).Population-based cohort study with age- and sex-stratified random sample of 927 men women aged 40-80 years followed over 20 (1990-2010).Rates arthroplasty (95% CI) were 17.7 (9.4-30.2) per 1,000 person-years in patients 5.3 (4.1-6.6) those without (P < 0.001). Type emerged as arthroplasty: hazard ratios CI), 3.8 (2.1-6.8) 0.001) unadjusted analysis 2.1 (1.1-3.8) = 0.023) after adjustment age, BMI,...
Vascular damage and platelet activation are associated with tissue remodeling in diseases such as systemic sclerosis, but the molecular mechanisms underlying this association have not been identified. In study, we show that serotonin (5-hydroxytryptamine [5-HT]) stored platelets strongly induces extracellular matrix synthesis interstitial fibroblasts via of 5-HT2B receptors (5-HT2B) a transforming growth factor β (TGF-β)–dependent manner. Dermal fibrosis was reduced 5-HT2B−/− mice using both...
Abstract Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, additional associations conditional false discovery rate approach. Many variants are also associated asthma six...
To investigate the efficacy of single and combined blockade tumor necrosis factor (TNF), interleukin-1 (IL-1), RANKL pathways on synovial inflammation, bone erosion, cartilage destruction in a TNF-driven arthritis model.Human TNF-transgenic (hTNFtg) mice were treated with anti-TNF (infliximab), IL-1 receptor antagonist (IL-1Ra; anakinra), or osteoprotegerin (OPG; an OPG-Fc fusion protein), either alone combinations 2 agents all 3 agents. Synovial damage evaluated histologically.Synovial...
Blocking TNF effectively inhibits inflammation and structural damage in human rheumatoid arthritis (RA). However, so far it is unclear whether the effect of a direct one or indirect on up-regulation other mediators. IL-1 may be these candidates because has central role animal models arthritis, inhibition used as therapy RA. We removed effects from TNF-mediated inflammatory joint disease by crossing IL-1alpha beta-deficient mice (IL-1-/-) with arthritic TNF-transgenic (hTNFtg) mice....
Abstract Objective To investigate the efficacy of a murine anti–interleukin‐6 receptor (anti–IL‐6R) antibody in directly blocking tumor necrosis factor (TNF)– and RANKL‐mediated osteoclastogenesis vitro vivo. Methods The against IL‐6R osteoclast differentiation mononuclear cells stimulated with RANKL was tested. In addition, arthritic human TNFα–transgenic mice were treated anti–IL‐6R antibody, formation bone erosion assessed paws. Results Blockade dose dependently reduced resorption...
Cardiac disease is a major contributor to disease-related death in Churg-Strauss syndrome (CSS). We conducted the current study determine prevalence and clinical impact of cardiac involvement CSS patients. performed multicenter, cross-sectional analysis patients diagnosed with CSS. workup included electrocardiography, echocardiography, magnetic resonance imaging (MRI), endomyocardial biopsy. analyzed 49 CSS: 22 had evidence involvement. A negative antineutrophil cytoplasmic antibodies (ANCA)...
The molecular mechanisms of syndesmophyte formation in ankylosing spondylitis (AS) are yet to be characterised. Molecules involved bone such as Wnt proteins and their antagonists probably drive AS.This study investigated sequential serum levels functional dickkopf-1 (Dkk1), a potent antagonist arthritis, by capture ELISA with its receptor LRP6 65 AS patients from the German Spondyloarthritis Inception Cohort. Dkk1 were then related structural progression (syndesmophyte formation) well...
Objective To study whether Dickkopf (DKK)-1, an inhibitor of wingless (Wnt) signalling, is involved in the fusion sacroiliac joints. Methods Mice transgenic for tumour necrosis factor (TNFtg mice), which develop bilateral sacroiliitis, were treated with vehicle, anti-TNF antibody or anti-DKK1 antibody. Sacroiliac joints analysed histological signs inflammation, bone erosion, osteoclast formation and ankylosis. Moreover, expression collagen type X, β-catenin DKK-1 was assessed by...
Abstract Objective Imatinib is a small‐molecule tyrosine kinase inhibitor capable of selective, dual inhibition the transforming growth factor β and platelet‐derived (PDGF) pathways. has previously been shown to prevent development inflammation‐driven experimental fibrosis when treatment was initiated before administration profibrotic stimulus. The aim this study confirm efficacy imatinib in murine model systemic sclerosis (SSc) that less driven by inflammation investigate whether also...
Introduction Inflammation is a major risk factor for systemic bone loss. Proinflammatory cytokines like tumour necrosis (TNF) affect homeostasis and induce It was hypothesised that impaired formation key component in inflammatory loss Dkk-1, Wnt antagonist, strong inhibitor of osteoblast-mediated formation.TNF transgenic (hTNFtg) mice were treated with neutralising antibodies against TNF, Dkk-1 or combination both agents. Systemic architecture analysed by histomorphometry. The expression...
We previously demonstrated the suppressive effects of regulatory T cells (Treg cells) on osteoclast differentiation in vitro. In this article, we show that blood markers bone resorption inversely correlate with amount circulating Treg healthy controls and rheumatoid arthritis patients, further suggesting may control destruction vivo. Indeed, marrow from Foxp3-transgenic (Foxp3tg) mice fully protected human TNF transgenic (hTNFtg) TNF-alpha-induced destruction, whereas Foxp3-deficient...
Abstract Objective Insufficient angiogenesis with tissue ischemia and accumulation of extracellular matrix are hallmarks systemic sclerosis (SSc). Based on the severely decreased oxygen levels in skin patients SSc, we aimed to investigate role hypoxia pathogenesis SSc. Methods Subtractive hybridization was used compare gene expression dermal fibroblasts under hypoxic normoxic conditions. Dermal were further characterized by exposure different concentrations for time periods as well...
Abelson kinase (c-abl) and platelet-derived growth factor (PDGF) are key players in the pathogenesis of systemic sclerosis (SSc). The aim present study was to evaluate antifibrotic potential dasatinib nilotinib, 2 novel inhibitors c-abl PDGF, which well tolerated have recently been approved. Dasatinib nilotinib dose-dependently reduced mRNA protein levels extracellular matrix proteins human stimulated dermal fibroblasts from SSc patients (IC(50) 0.5-2.0 nM for 0.8-2.5 nilotinib). In a mouse...
T-helper type 2 responses are crucial in Churg-Strauss syndrome (CSS) and may enhance the production of IgG4 antibodies. The authors assessed immune response CSS patients.The included 46 consecutive patients with (24 active 22 quiescent disease), 26 granulomatosis polyangiitis (GPA, Wegener's), 25 atopic asthma 20 healthy controls determined serum IgG, IgM, IgA, IgE IgG subclass levels. Tissue infiltration by plasma cells was nine CSS, 10 GPA, chronic sinusitis (11 11 without...