
Wolfgang BaumUniversitätsklinikum Erlangen
Wolfgang Baum
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Publications (58)
The downstream regulatory element antagonist modulator (DREAM) modulates ion channel function and gene transcription. Functionally, DREAM is implicated in physiological and pathological processes including cell proliferation, inflammation, and nociception. Despite its multiple functions and robust expression in forebrain tissue, neurons and glial c...
Systemic immune dysregulation contributes to the development of neuropsychiatric and neurodegenerative diseases. The precise effect of chronic peripheral immune stimulation on myeloid cells across anatomical brain regions is unclear. Here, we demonstrate brain-region-specific differences in myeloid responses induced by chronic peripheral inflammati...
Closed circulatory systems (CCS) underlie the function of vertebrate organs, but in long bones their structure is unclear, although they constitute the exit route for bone marrow (BM) leukocytes. To understand neutrophil emigration from BM, we studied the vascular system of murine long bones. Here we show that hundreds of capillaries originate in B...
Background:
ADAMTS aggrecanases play a major role in cartilage degeneration during degenerative and inflammatory arthritis. The cartilage-specific secreted protein Upper zone of growth plate and cartilage matrix associated protein (Ucma) has been shown to block ADAMTS-triggered aggrecanolysis in experimental osteoarthritis. Here we aimed to invest...
The prevalence of neurodegenerative disease and arthritis increases with age. Despite both processes being associated with immune activation and inflammation, little is known about the mechanistic interactions between neurodegenerative disease and arthritis. In this article, we show that tau-transgenic (tau-tg) mice that develop neurodegenerative d...
Although articular cartilage degeneration represents a major public health problem, the underlying molecular mechanisms are still poorly characterized. We have previously utilized genome-wide expression analysis to identify specific markers of porcine articular cartilage, one of them being Thrombospondin-4 (Thbs4). In the present study we analyzed...
Chronic peripheral inflammation mediated by cytokines such as TNFα, IL-1β, and IL-6 is associated with psychiatric disorders like depression and anxiety. However, it remains elusive which distinct type of peripheral inflammation triggers neuroinflammation and affects hippocampal plasticity resulting in depressive-like behavior. We hypothesized that...
Immunglobulin G (IgG) sialylation represents a key checkpoint that determines the engagement of pro- or anti-inflammatory Fcγ receptors (FcγR) and the direction of the immune response. Whether IgG sialylation influences osteoclast differentiation and subsequently bone architecture has not been determined yet, but may represent an important link bet...
One feature of the AP-1 transcription factor family is their ability to regulate inflammatory processes and the activation and formation of osteoclasts. To test whether AP-1 expression is involved in rheumatoid arthritis (RA), serum K/BxN transfer model (SIA) is used. At the molecular levels, AP-1 expression analyses in wildtype joints show increas...
Objective:
Rheumatoid arthritis therapies that are based on inhibition of a single cytokine, e.g., tumor necrosis factor α (TNFα) or interleukin-6 (IL-6), produce clinically meaningful responses in only about half of the treated patients. This study was undertaken to investigate whether combined inhibition of TNFα and IL-17 has additive or synergi...
Background
The overexpression of tumor necrosis factor (TNF)-α leads to systemic as well as local loss of bone and cartilage and is also an important regulator during fracture healing. In this study, we investigate how TNF-α inhibition using a targeted monoclonal antibody affects fracture healing in a TNF-α driven animal model of human rheumatoid a...
Infection 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 brasiliensis influence rheumatoid arthritis development as well as the molecular mechanism from Th2 and eosinophil cells in this effect.
5 to 7...
Dendritic cells (DCs) are essential for the initiation of synovial inflammation, but it is unclear which subset of DCs performs this task. We have shown that FMS-like tyrosine kinase 3 ligand (Flt3L)-dependent DCs are important for disease development in a mouse model for RA. However since Flt3L-/- mice have reductions in all conventional (c)DCs it...
Background Our 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 production of matrix metalloproteinases by synovial fibroblasts. Furthermore, S100A4 stimulates synthesis of tumou...
Objective
To test whether inhibition of sclerostin by a targeted monoclonal antibody (Scl-Ab) protects from bone and cartilage damage in inflammatory arthritis. Sclerostin is a potent inhibitor of bone formation and may be responsible for the low level of bone repair in patients with rheumatoid arthritis.
Methods
Human tumour necrosis factor trans...
Background Our 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 production of matrix metalloproteinases by synovial fibroblasts. Furthermore, S100A4 stimulates synthesis of tumou...
Autoimmunity is complicated by bone loss. In human rheumatoid arthritis (RA), the most severe inflammatory joint disease, autoantibodies against citrullinated proteins are among the strongest risk factors for bone destruction. We therefore hypothesized that these autoantibodies directly influence bone metabolism. Here, we found a strong and specifi...
Osteophyte formation is a common phenomenon in arthritis. Bone formation by endochondral ossification is considered a key pathophysiological process in the formation of osteophytes.
To examine the hypothesis that inhibition of smoothened (Smo), a key component of the hedgehog pathway inhibits osteophyte formation as the hedgehog pathway mediates en...
Background Radon therapy as alternative therapy for rheumatic diseases in curative tunnels such as the Heilstollen Bad Gastein in Austria has been reported to reduce pain and amount of drug usage [1,2]. Inhaled radon remains in the body as decaying radioactive radon progeny, and exhibits analgesic and anti-inflammatory effects [3]. In the Heilstoll...
Tumour necrosis factor alpha (TNF-α) is a major inducer for inflammation and bone loss. Here, we investigated whether interleukin (IL)-17 plays a role in TNF-α-mediated inflammation and bone resorption. Human TNF-α transgenic (hTNFtg) mice were treated with a neutralizing anti-IL-17A antibody and assessed for inflammation, cartilage and bone damage...
The proteasome inhibitor bortezomib has potent anti-myeloma and bone-protective activity. Recently, bortezomib was shown to directly inhibit osteoclastogenesis. The aim of this study was to analyze the influence and therapeutic effect of bortezomib in a mouse model of inflammatory arthritis.
Heterozygous human tumor necrosis factor α (hTNFα)-transg...
Reduced vitamin D intake has been linked to increased susceptibility to develop rheumatoid arthritis (RA) and vitamin D deficiency is associated with increased disease activity in RA patients. The pathophysiological role of vitamin D in joint inflammation is, however, unclear.
To determine the influence of absent vitamin D signalling in chronic art...
Introduction Inflammation is a major risk factor for systemic bone loss. Proinflammatory cytokines like tumour necrosis factor (TNF) affect bone homeostasis and induce bone loss. It was hypothesised that impaired bone formation is a key component in inflammatory bone loss and that Dkk-1, a Wnt antagonist, is a strong inhibitor of osteoblast-mediate...
Mice overexpressing Fra-1 and hTNF showed increased clinical arthritis scores as compared to hTNFtg mice. Histological analysis showed an increase of synovial inflammation in Fra-1tgxhTNFtg mice. These mice had virtually no synovial bone erosions and showed enhanced osteoblast function and matrix deposition compared to hTNFtg mice. Interestingly, c...
Heterozygous human tumour necrosis factor α transgenic (hTNFαtg) mice and wild-type littermates were intravenously injected with 0.75 mg/kg bortezomib or phosphate buffered saline twice a week. Mice were weekly assessed for clinical signs of arthritis. After 6 weeks of …
Nitrogen-containing bisphosphonates (N-BPs) are effective antiosteolytic agents in patients with multiple myeloma. Preclinical studies have also demonstrated that these agents have direct antitumor effects in vitro and can reduce tumor burden in a variety of animal models, although it is not clear whether such effects are caused by direct actions o...
Chronic inflammation is a major risk factor for systemic bone loss leading to osteoporotic fracture and substantial morbidity and mortality. Inflammatory cytokines, particularly tumour necrosis factor (TNF) and interleukin-1 (IL1), are thought to play a key role in the pathogenesis of inflammation-induced bone loss, but their exact roles are yet to...
Crescentic glomerulonephritis (crGN) is a frequent and life-threatening manifestation of antineutrophil cytoplasmatic antibody-associated vasculitis. Up-regulation of proinflammatory cytokines contributes to renal damage by activation of p38 mitogen-activated protein kinases (MAPKs). However, it is unclear which of the four p38MAPK isoforms are exp...
Annexins are characterized by the ability to bind phospholipids of membranes in the presence of Ca2+. Annexin A5 represents a typical member of this protein family and is a natural occurring highly specific ligand for phosphatidylserine (PS). The exposure of PS is one major "eat me" signal for phagocytes of apoptotic and necrotic cells. Apoptotic c...
Apoptotic and necrotic cells expose phosphatidylserine (PS). This membrane modification ensures a swift recognition and uptake by phagocytes of the dying and dead cells. Annexin V (AxV) preferentially binds to anionic phospholipids and thereby, modulates the clearance process. First, we analyzed the influence of AxV on the immunogenicity of apoptot...
The mammalian target of rapamycin (mToR) plays a crucial role in cell growth due to its role as nutrient dependent regulator of important cytokine signalling pathways. In multiple myeloma (MM) mToR is involved in the AKT pathway which can be activated by the loss of the tumor suppressor PTEN or stimulation with growth and survival factors such as i...
In recent years there has been significant progress in the application of process mineralogy to metallurgical challenges in the minerals industry mainly because of the increased availability and improvement of SEM-based automated systems for acquiring quantitative mineralogical data. This progress combined with advances in analysis, data visualizat...
Cytokines of the gp130 family, particularly interleukin 6 (IL-6), play a central role in the growth and survival of malignant plasma cells. Recently, novel neurotrophin-1 (NNT-1)/B cell-stimulating factor-3 (BSF-3), also reported as cardiotrophin-like cytokine (CLC), was identified as a cytokine belonging to the gp130 family. BSF-3, similar to IL-6...
A concentrator survey was performed to quantify the influence of copper and gangue mineralogy on metallurgical performance and to identify specific optimization areas of the circuit. All samples were subjected to a combination of QEMSCAN automated mineral analysis to establish a size-by-size mineralogical and metallurgical testing. The mineralogica...
A procedure was developed to generate recombinant single chain Fv (scFv) antibody fragments reacting with the extracellular domain of human cell surface antigen CD13 (hCD13; aminopeptidase N) on intact cells. Membrane fractions prepared from a stably transfected hCD13-positive murine NIH/3T3 cell line were used to immunize BALB/c mice, with the int...
Cytokines of the gp130-family, particularly interleukin(IL)-6, play a crucial role in the propagation of malignant plasma cells.
The role of IL-6 and other gp130-cytokines was studied in the human plasma cell line INA-6 in vitro and in INA-6 xenografts. The proliferative response to gp130-cytokines was evaluated and activated components of gp130-si...
Introduction: Cytokines of the gp130-family, particularly interleukin(IL)-6, play a crucial role in the propagation of malignant plasma cells. Materials and methods: The role of IL-6 and other gp130-cytokines was studied in the human plasma cell line INA-6 in vitro and in INA-6 xenografts. The proliferative response to gp130-cytokines was evaluated...
The growth of malignant plasma cells in vitro is regulated in particular by cytokines of the interleukin(IL)-6 family. While IL-6 itself has been shown to be an important growth factor in vivo, the roles of the other members of this family remain to be elucidated. Our aim was to develop a preclinical tumor model for human multiple myeloma to study...
Human T-cell acute lymphocytic leukaemia (ALL) was established in athymic nude or severe combined immunodeficient (SCID) mice by injecting CEM or MOLT-16 cells. When nude mice bearing approx. 2 g of tumour were treated with a single injection of CD7 antibody TH-69, 82.6% reached complete remission within 10 d whereas 13.0% showed partial remission....
Inflammatory joint diseases exhibit distinct pathohistological and immunological characteristics. The studies performed demonstrated that in comparison to normal controls peripheral blood mononuclear cells from patients with rheumatoid arthritis (RA) presented an increased percentage of monocytic cells. Peripheral blood mononuclear cells from patie...
Binding of various polysaccharides and (neo)glycoproteins can be observed in gastrointestinal tissue. Most of the substances bind both to neoplastic and inflammatory tissue.The epithelium of human gastrointestinal tumors was found to be heterogeneous with regard to the binding of the analyzed polysaccharides and (neo)glycoproteins. A pronounced lab...
The objective of the present investigation was to culture helper or suppressor/cytotoxic T cell subsets after extensive purification in interleukin 2-containing medium to determine whether phenotype changes for OKT4/91d6- or OKT8/Leu-2a-defined antigens do occur with prolonged culture. Repeated and sequential analysis of such polyclonally activated...