Georg Schett

Friedrich-Alexander-University of Erlangen-Nürnberg, Erlangen, Bavaria, Germany

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Publications (471)3372.49 Total impact

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    ABSTRACT: The effect of metabolic stress on the bone marrow microenvironment is poorly defined. We show that high-fat diet (HFD) decreased long-term Lin(-)Sca-1(+)c-Kit(+) (LSK) stem cells and shifted lymphoid to myeloid cell differentiation. Bone marrow niche function was impaired after HFD as shown by poor reconstitution of hematopoietic stem cells. HFD led to robust activation of PPARγ2, which impaired osteoblastogenesis while enhancing bone marrow adipogenesis. At the same time, expression of genes such as Jag-1, SDF-1, and IL-7 forming the bone marrow niche was highly suppressed after HFD. Moreover, structural changes of microbiota were associated to HFD-induced bone marrow changes. Antibiotic treatment partially rescued HFD-mediated effects on the bone marrow niche, while transplantation of stools from HFD mice could transfer the effect to normal mice. These findings show that metabolic stress affects the bone marrow niche by alterations of gut microbiota and osteoblast-adipocyte homeostasis.
    Cell metabolism 09/2015; DOI:10.1016/j.cmet.2015.08.020 · 17.57 Impact Factor
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    ABSTRACT: Background: Pasteurella multocida toxin (PMT) is a potent inducer of osteoclast formation. Pigs suffering from an infection with toxigenic Pasteurella multocida strains develop atrophic rhinitis characterised by a loss of turbinate bones and conchae. However, on the molecular level the process of bone loss remains largely uncharacterised. Results: Recently it was found that PMT activates the serine/threonine kinase mammalian target of rapamycin (mTOR) in fibroblasts. Using RAW264.7 macrophages, we investigated the role of the mTOR complex 1 (mTORC1) in PMT-mediated osteoclast formation. PMT induces the differentiation of RAW264.7 macrophages into multinucleated, tartrate resistant acid phosphatase (TRAP) positive osteoclasts that are capable to resorb bone. In the presence of the mTORC1 inhibitor rapamycin, PMT was significantly less able to induce the formation of TRAP-positive osteoclasts. Accordingly, the resulting resorption of bone was strongly reduced. A major target of mTOR is the 70 kDa ribosomal protein S6 kinase 1 (p70 S6K1). Activated p70 S6K1 decreases the expression of programmed cell death protein 4 (PDCD4), a negative transcriptional regulator of osteoclastogenesis, at the protein and gene level. Ultimately this results in the activation of c-Jun, a component of the activator protein 1 (AP-1) complex, which is a major transcription factor for the induction of osteoclast-specific genes. We now demonstrate that c-Jun and its downstream target, the osteoclast-specific bone degrading protease cathepsin K, are upregulated upon PMT treatment in an mTOR-dependent manner. Conclusions: Activation of mTOR signalling plays a central role in the formation of osteoclasts through the bacterial toxin PMT. On the molecular level, PMT-induced activation of mTOR leads to down regulation of PDCD4, a known repressor of AP-1 complex, culminating in the activation of c-Jun, an essential transcription factor for triggering osteoclastogenesis.
    Cell Communication and Signaling 09/2015; 13(40). DOI:10.1186/s12964-015-0117-7 · 3.38 Impact Factor
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    ABSTRACT: Objective: To determine the role of overexpression of the AP-1 transcription factor Fra-1 (Fra-1tg) in adipose-derived stromal cells (ADSCs) as therapeutic treatment of collagenase-induced osteoarthritis (OA). Methods: OA was induced by injection of collagenase into knee joints of C57BL/6 male mice. Wildtype or Fra-1tg ADSCs were isolated from inguinal fat pads of 8 week-old mice, and injected into knee joints 7 days after OA induction. Histological analyses on cartilage destruction and chondrocyte cell death were performed. Adipogenic differentiation capacity was investigated, and gene expression- and cytokine-profiling was performed in stromal vascular fractions (SVFs) and ADSCs. Results: OA related cartilage destruction and chondrocyte cell death were significantly reduced in knee joints treated with Fra-1tg ADSCs compared with knee joints treated with wt ADSCs. This effect did not result from the higher number of adipogenic progenitors observed in SVFs from Fra-1tg compared to wildtype fat pads, since injection of wildtype ADSCs enriched for adipogenic progenitors did not show any additional chondroprotective effects compared to unsorted ADSCs. However, Fra-1tg ADSCs showed a decreased adipogenic differentiation capacity. Moreover, Fra-1 significantly inhibited the pro-inflammatory IL-6 and pentraxin-3 expression, while increasing the expression of extracellular matrix proteins, such as periostin and F-spondin1. These findings suggest that Fra-1 over-expression leads to an increased chondroprotective effect of ADSCs in OA. Conclusion: ADSCs overexpressing Fra-1 effectively protect from OA. Our data indicate that genetic modifications of ADSCs, such as Fra-1 overexpression, may improve their potential to protect articular cartilage from OA-mediated damage. This article is protected by copyright. All rights reserved.
    Arthritis and Rheumatology 09/2015; DOI:10.1002/art.39425
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    ABSTRACT: Kv1.3 and IKCa1 lymphocyte potassium channels have been implicated as important targets of selective immunomodulation. We compared the alterations in cytokine production upon selective inhibition of Kv1.3 or IKCa1 channels (by MGTX and TRAM, respectively) in healthy donors (HD), RA and AS patients. We also determined calcium influx kinetics and its sensitivity to Kv1.3 and IKCa1 channel inhibition following PHA activation in CD4, Th1, Th2 and CD8 cells as well as monocytes. The application of TRAM resulted in a lower production of TNF-a and IL1-RA in all three study groups. Inhibition by TRAM had contrary effects on the production of IL-1b and IL-5: While their production was increased by PBMCs of RA patients, this effect was not observed in HD and AS PBMCs. While treatment with MGTX resulted in a similar decrease in calcium influx in the CD4 and Th2 subsets across all study groups, TRAM treatment had opposite effects on RA and HD samples: It decreased calcium influx in the Th2 and CD8 subsets in RA, while only Th1 cells were affected in HDs. The effects of IKCa1 channel inhibition are controversial in samples of RA and AS patients, since it shifts the inflammatory balance into the pro-inflammatory direction.
    Immunologic Research 08/2015; DOI:10.1007/s12026-015-8683-8 · 3.10 Impact Factor
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    ABSTRACT: Osteoporosis can arise in systemic lupus erythematosus (SLE) patients secondary to medication and/or chronic inflammation. To analyze if patients with SLE have phenotypically-impaired osteoclastogenesis, we differentiated ex vivo monocytes from 72 SLE patients and 15 healthy individuals into osteoclasts followed by TRAP staining and counting. We identified a subgroup of SLE patients (45%) with a significantly impaired osteoclast differentiation, relative to the other SLE patients or healthy individuals (OR 11.2; 95% CI 1.4-89.9). A review of medication indicated that patients with osteoclast counts equal to healthy donors were significantly more likely to be treated with mycophenolate mofetil (MMF) compared to patients with impaired osteoclastogenesis. We analyzed expression of RANKL and the MMF target genes IMPDH1 and IMPDH2 in osteoclasts by qPCR, but detected no difference. Since MMF might influence interferon-α (IFNα) and -γ (IFNγ) we measured serum IFNα and IFNγ levels. Patients with very low osteoclast counts also had comparably higher IFNα serum levels than patients with normal osteoclast counts. We conclude that in vitro osteoclastogenesis is impaired in a subgroup of SLE patients. This correlates inversely with MMF treatment and high IFNα serum levels. Further observational study will be required to determine whether this translates into a clinically meaningful effect.
    International Journal of Molecular Sciences 08/2015; 16(8):18825-35. DOI:10.3390/ijms160818825 · 2.86 Impact Factor
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    ABSTRACT: This review summarises recent evidence about the interaction between bone, the immune system and cartilage in disabling conditions such as osteoarthritis, rheumatoid arthritis and spondyloarthritis. These topics have been recently discussed at the ‘OsteoRheumatology’ conference held in Genoa in October 2014. The meeting, at its 10th edition, has been conceived to bring together distinguished international experts in the fields of rheumatic and metabolic bone diseases with the aim of discussing emerging knowledge regarding the role of the bone tissue in rheumatic diseases. Moreover, this review focuses on new treatments based on underlying the pathophysiological processes in rheumatic diseases. Although, a number of issues still remain to be clarified, it seems quite clear that in clinical practice, as well as in basic and translational research, there is a need for more knowledge of the interactions between the cartilage, the immune system and the bone. In this context, ‘OsteoRheumatology’ represents a potential new discipline providing a greater insight into this interplay, in order to face the multifactorial and complex issues underlying common and disabling rheumatic diseases.
    08/2015; 1(Suppl 1):e000083. DOI:10.1136/rmdopen-2015-000083
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    ABSTRACT: To monitor size and shape changes of bone erosions and changes in BMD in the vicinity of the erosion and in the periarticular trabecular compartment of patients with RA using high-resolution peripheral quantitative CT (HR-pQCT) imaging and to compare an automated three-dimensional (3D) image processing technique with manual measurements of erosion width and depth. The shape of 40 bone erosions and composition of bone around the erosions were analysed in the MCP joints of 22 RA patients both manually and by semi-automated 3D image processing at two different time points. Periosteal segmentation was performed using volume growing and morphological operations. Image registration was applied for transfer of baseline segmentations to follow-up datasets. Eight erosions decreased in size, 6 increased and 28 remained stable. Increasing erosions were more spherical and smaller at baseline compared with decreasing or stable erosions. BMD in the vicinity of shrinking erosions increased, while it decreased next to expanding erosions. There was moderate agreement in the determination of erosion volume between semi-automated and manual measurements, but agreement was poor when assessing changes in volume over time. Longitudinal changes in erosion size and shape and of BMD in the vicinity of an erosion can be measured. BMD changes are associated with progression and regression of erosions. However, the semi-automated and manual approaches did not classify longitudinal changes of erosion volume in the same way. Further research is necessary to define the nature of these differences. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email:
    Rheumatology (Oxford, England) 07/2015; DOI:10.1093/rheumatology/kev256 · 4.48 Impact Factor
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    ABSTRACT: Objectives Autophagy has recently been shown to regulate osteoclast activity and osteoclast differentiation. Here, we aim to investigate the impact of autophagy inhibition as a potential therapeutic approach for the treatment of osteoporosis in preclinical models. Methods Systemic bone loss was induced in mice by glucocorticoids and by ovariectomy (OVX). Autophagy was targeted by conditional inactivation of autophagy-related gene 7 (Atg7) and by treatment with chloroquine (CQ). Bone density was evaluated by microCT. The role of autophagy on osteoclastogenesis was analysed by osteoclastogenesis and bone resorption assays. The quantification of receptor activator of nuclear factor κ B ligand and osteoprotegerin proteins in cocultures was performed using ELISA whereas that of osteoclast and osteoblast differentiation markers was by qPCR. Results Selective deletion of Atg7 in monocytes from Atg7fl/fl_x_LysM-Cre mice mitigated glucocorticoid-induced and OVX-induced osteoclast differentiation and bone loss compared with Atg7fl/fl littermates. Pharmacological inhibition of autophagy by treatment with CQ suppressed glucocorticoid-induced osteoclastogenesis and protected mice from bone loss. Similarly, inactivation of autophagy shielded mice from OVX-induced bone loss. Inhibition of autophagy led to decreased osteoclast differentiation with lower expression of osteoclast markers such as NFATc1, tartrate-resistant acid phosphatase, OSCAR and cathepsin K and attenuated bone resorption in vitro. In contrast, osteoblast differentiation was not affected by inhibition of autophagy. Conclusions Pharmacological or genetic inactivation of autophagy ameliorated glucocorticoid-induced and OVX-induced bone loss by inhibiting osteoclastogenesis. These findings may have direct translational implications for the treatment of osteoporosis, since inhibitors of autophagy such as CQ are already in clinical use.
    Annals of the rheumatic diseases 06/2015; DOI:10.1136/annrheumdis-2015-207240 · 10.38 Impact Factor
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    ABSTRACT: To analyze the glycosylation of anti-β2GP1, we investigated purified IgG from healthy children, patients with APS, and asymptomatic adult carriers of antiphospholipid antibodies. We observed that in the sera of healthy children and of patients with APS, IgG3 and IgG2 were predominant, respectively. The potentially protective anti-β2GP1-IgM was lower in the sera of healthy children. Although anti-β2GP1-associated C1q did not differ between children and patients with antiphospholipid syndrome, the associated C3c was significantly higher in the sera of healthy children. This indicates a more efficient clearance of anti-β2GP1 immune complexes in the healthy children. This clearance is not accompanied by inflammation or coagulatory events. It is likely that the most important pathogenic factor of the anti-β2GP1-IgG is related to the different glycosylation observed in healthy and diseased individuals. We detected a significantly higher sialylation of anti-β2GP1-IgG isolated from the sera of healthy children and asymptomatic adults when compared with that of patients with clinically apparent antiphospholipid syndrome. Low sialylated IgG reportedly ameliorates inflammation and inflammation promotes hyposialylation. Thus, both reactions create a vicious circle that precipitates the pathology of the antiphospholipid syndrome including thrombus-formation. We conclude that the increased sialylation of anti-β2GP1-IgG of sera of healthy individuals limits their pathogenicity.
    Journal of Immunology Research 06/2015; 2015(Article ID 638129):12. DOI:10.1155/2015/638129 · 2.93 Impact Factor
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    ABSTRACT: 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 chronic peripheral inflammation in the human TNF-α transgenic (TNFtg) mouse model of rheumatoid arthritis spreads into the central nervous system and induces depressive state manifested in specific behavioral pattern and impaired adult hippocampal neurogenesis. TNFtg mice showed severe erosive arthritis with increased IL-1β and IL-6 expression in tarsal joints with highly elevated human TNF-α levels in the serum. Intriguingly, IL-1β and IL-6 mRNA levels were not altered in the hippocampus of TNFtg mice. In contrast to the pronounced monocytosis in joints and spleen of TNFtg mice, signs of hippocampal microgliosis or astrocytosis were lacking. Furthermore, locomotion was impaired, but there was no locomotion-independent depressive behavior in TNFtg mice. Proliferation and maturation of hippocampal neural precursor cells as well as survival of newly generated neurons were preserved in the dentate gyrus of TNFtg mice despite reduced motor activity and peripheral inflammatory signature. We conclude that peripheral inflammation in TNFtg mice is mediated by chronic activation of the innate immune system. However, severe peripheral inflammation, though impairing locomotor activity, does not elicit depressive-like behavior. These structural and functional findings indicate the maintenance of hippocampal immunity, cellular plasticity, and behavior despite peripheral innate inflammation. Copyright © 2015. Published by Elsevier Inc.
    Brain Behavior and Immunity 06/2015; 49. DOI:10.1016/j.bbi.2015.05.011 · 5.89 Impact Factor
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    ABSTRACT: Osteoarthritis is not only characterized by cartilage degradation but also involves subchondral bone remodeling and osteophyte formation. Osteophytes are fibrocartilage-capped bony outgrowths originating from the periosteum. The pathophysiology of osteophyte formation is not completely understood. Yet, different research approaches are under way. Therefore, a histological osteophyte classification to achieve comparable results in osteophyte research was established for application to basic science research questions. The osteophytes were collected from knee joints of osteoarthritis patients (n=10, 94 osteophytes in total) after joint replacement surgery. Their size and origin in the respective joint were photo-documented. To develop an osteophyte classification, serial tissue sections were evaluated using histological (hematoxylin and eosin, Masson's trichrome, toluidine blue) and immunohistochemical staining (collagen type II). Based on the histological and immunohistochemical evaluation, osteophytes were categorized into four different types depending on the degree of ossification and the percentage of mesenchymal connective tissue. Size and localization of osteophytes were independent from the histological stages. This histological classification system of osteoarthritis osteophytes provides a helpful tool for analyzing and monitoring osteophyte development and for characterizing osteophyte types within a single human joint and may therefore contribute to achieve comparable results when analyzing histological findings in osteophytes. Copyright © 2015 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.
    Joint, bone, spine: revue du rhumatisme 06/2015; DOI:10.1016/j.jbspin.2015.04.008 · 2.90 Impact Factor
  • Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):350.2-351. DOI:10.1136/annrheumdis-2015-eular.2907 · 10.38 Impact Factor
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    ABSTRACT: Type 2 innate lymphoid cells (ILC2s), a recently identified population of lymphoid cells lacking lineage-specific receptors, promote type 2 immunity and tissue remodelling. However, the contributive role of ILC2s in the pathogenesis of systemic sclerosis (SSc) is unknown. We aimed to evaluate the levels and correlations with fibrotic manifestations in SSc. 69 patients with SSc and 47 healthy controls were included. Blood samples and skin sections were analysed by flow cytometry and immunohistochemically by staining two complementary panels of markers. Dermal and circulating ILC2s were significantly elevated in patients with SSc compared with controls. Dermal, but not circulating ILC2s were activated. Stratification of the SSc population in patients with limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) demonstrated increased levels of ILC2s in both subgroups with significantly higher frequencies in dcSSc compared with lcSSc. Moreover, dermal and circulating ILC2 counts correlated closely with the modified Rodnan skin score and with the presence of pulmonary fibrosis. ILC2 counts are elevated in patients with SSc and correlate with the extent of skin fibrosis and the presence of interstitial lung disease providing compelling evidence for profibrotic effect of ILC2s in SSc. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to
    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):956.2-956. DOI:10.1136/annrheumdis-2015-eular.4060 · 10.38 Impact Factor
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    ABSTRACT: Molecular and clinical observations provide evidence for a potential role of parathyroid hormone (PTH) in colorectal cancer development. We therefore aimed to assess the association of PTH with regard to colorectal cancer precursor lesions. A cohort of 1432 participants, 777 men, 58.4 ± 9.6 years and 701 women, 59.1 ± 10.6 years, undergoing screening colonoscopy were allocated to PTH serum concentrations either above or below 55 ng/L. The number, localization, size, and histology of the polypoid lesions detected during screening colonoscopy were recorded according to PTH serum concentrations. Serum PTH concentrations were not different between men and women. Women with PTH serum concentrations above the cut-off had significantly more adenomas (13/40; 32.5 %) of the distal colon compared to women below the cut-off (91/659; 13.8 %; P = 0.001). Additionally, the rate of dysplasia in adenomas of the distal colon was higher in women with high compared to low PTH concentrations (P = 0.001). These findings remained robust after adjustments for serum vitamin D, age, plasma creatinine, BMI, diabetes, and liver steatosis. No associations were observed between serum PTH concentrations and colorectal lesions in men. These data suggest that elevated PTH serum concentrations might have a role in colorectal cancer development as indicated by higher rates of adenomas, specifically with dysplasia, in women. The role of PTH in colon carcinogenesis and its sex specificity deserve further study.
    Hormones and Cancer 05/2015; 6(4). DOI:10.1007/s12672-015-0227-0 · 0.02 Impact Factor
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    ABSTRACT: Clustering of surface receptors is often required to initiate signal transduction, receptor internalization, and cellular activation. To study the kinetics of clustering, we developed an economic high-throughput method using flow cytometry. The quantification of receptor clustering by flow cytometry is based on the following two observations: first, the fluorescence signal length (FL time-of-flight [ToF]) decreases relative to the forward scatter signal length (FSc-ToF), and second, the peak FL (FL-peak) increases relative to the integral FL (FL-integral) upon clustering of FL-labeled surface receptors. Receptor macroclustering can therefore be quantified using the ratios FL-ToF/FSc-ToF (method ToF) or FL-peak/FL-integral (method Peak). We have used these methods to analyze clustering of two immune receptors known to undergo different conformational and oligomeric states: the BCR and the complement receptor 3 (CR3), on murine splenocytes, purified B cells, and human neutrophils. Engagement of both the BCR and CR3, on immortalized as well as primary murine B cells and human neutrophil, respectively, resulted in decreased FL-ToF/FSc-ToF and increased FL-peak/FL-integral ratios. Manipulation of the actin-myosin cytoskeleton altered BCR clustering which could be measured using the established parameters. To confirm clustering of CR3 on neutrophils, we applied imaging flow cytometry. Because receptor engagement is as a biological process dependent on cell viability, energy metabolism, and temperature, receptor clustering can only be quantified by gating on viable cells under physiological conditions. In summary, with this novel method, receptor clustering on nonadherent cells can easily be monitored by high-throughput conventional flow cytometry. Copyright © 2015 by The American Association of Immunologists, Inc.
    The Journal of Immunology 05/2015; 195(1). DOI:10.4049/jimmunol.1401889 · 4.92 Impact Factor
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    ABSTRACT: Neutrophil granulocytes possess a large arsenal of pro-inflammatory substances and mechanisms that empower them to drive local acute immune reactions to invading microorganisms or endogenous inflammatory triggers. The use of this armory needs to be tightly controlled to avoid chronic inflammation and collateral tissue damage. In gout, inflammation arises from precipitation of uric acid in the form of needle-shaped monosodium urate crystals. Inflammasome activation by these crystals in local immune cells results in a rapid and dramatic recruitment of neutrophils. This neutrophil influx is accompanied by the infamously intense clinical symptoms of inflammation during an acute gout attack. Neutrophilic inflammation however is equipped with a built-in safeguard; activated neutrophils form neutrophil extracellular traps (NETs). At the very high neutrophil densities that occur at the site of inflammation, NETs build aggregates that densely pack the monosodium urate (MSU) crystals and trap and degrade pro-inflammatory mediators by inherent proteases. Local removal of cytokines and chemokines by aggregated NETs explains how acute inflammation can stop in the consistent presence of the inflammatory trigger. Aggregated NETs resemble early stages of the typical large MSU deposits that constitute the pathognomonic structures of gout, tophi. Although tophi contribute to muscosceletal damage and mortality in patients with chronic gout, they can therefore be considered as a payoff that is necessary to silence the intense inflammatory response during acute gout.
    Journal of Molecular Medicine 05/2015; 93(7). DOI:10.1007/s00109-015-1295-x · 5.11 Impact Factor
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    ABSTRACT: TNF-α drives bone destruction but also inhibits new bone formation by inducing Dkk-1, an inhibitor of the Wnt pathway. Accordingly, blocking Dkk-1 reverses the bone-destructive phenotype to a bone-forming pattern in experimental arthritis. To delineate the potential role of Dkk-1 in the structural phenotype of human arthritis, we analyzed the expression of Dkk-1 and its regulation by pro-inflammatory cytokines in spondyloarthritis (SpA) versus rheumatoid arthritis (RA) inflamed peripheral joints. Expression of Dkk-1 and pro-inflammatory cytokines was determined by ELISA and microarray in synovial fluid (SF) and tissue, respectively. Regulation of Dkk-1 production by pro-inflammatory cytokines was assessed in fibroblast-like synoviocytes (FLS) cultures. TNF-α and IL-1β, but not IL-6, levels were significantly higher in RA than SpA SF (p<0.001 for both). SF levels of Dkk-1 were similar in SpA and RA, and did not correlated with TNF-α and IL-1β levels. However, Dkk-1 showed an inverse correlation with IL-6 levels in both SpA (r =-0.31; p=0.04) and RA SF (r=-0.39; p=0.01), which was reproduced at the mRNA levels in synovial tissue. In vitro experiments with FLS confirmed that Dkk-1 production was strongly induced by TNF-α but clearly suppressed by IL-6. Moreover, IL-6 was able to suppress the TNF-α-induced upregulation of Dkk-1 production by FLS. The inverse correlation of Dkk-1 with IL-6 levels observed in vivo in the inflamed joints was mirrored by the differential regulation of Dkk-1 production by TNF-α and IL-6 in vitro. The relative balance between these and other factors in the arthritic joints may determine functional Wnt signalling and tissue remodelling. This article is protected by copyright. All rights reserved. © 2015, American College of Rheumatology.
    Arthritis and Rheumatology 05/2015; DOI:10.1002/art.39183
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    ABSTRACT: To investigate the prevalence of knee US findings of inflammation and structural damage in aged individuals (≥60 years) of a long-term population-based cohort and to correlate these findings with demographic, clinical and laboratory parameters. Cross-sectional clinical and US investigation of both knee joints during the 2010 follow-up of the prospective population-based Bruneck Study. Demographic variables, physical activity, comorbidities, medications, pain, and functional scales related to the knee joints were recorded. US-assessed parameters were synovial hypertrophy, power Doppler signal, joint effusion, cartilage abnormalities, osteophytes, enthesopathy and bursitis. Statistics included univariate and multivariate regression analysis. A total of 488 subjects (mean age 72.5 years; 53.5% females, 46.5% males) were examined by clinical assessment, and 433 of these underwent US examination of both knees. Both inflammatory and structural abnormalities were found in 296 (68.8%) subjects. Inflammatory abnormalities were significantly associated with age in years, male gender, diabetes and the presence of knee joint symptoms. In the multivariate analysis, age, male gender and knee swelling emerged as independent predictors of inflammation [odds ratio (OR) (95% CI) = 1.06 (1.03, 1.09), 2.55 (1.55, 4.21) and 5.92 (1.99, 17.58), respectively]. The present study showed a high prevalence of US inflammatory abnormalities in the knee joints of a normal aged population. These data suggest a substantial contribution of inflammation in progressive impairment of joint function with age. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email:
    Rheumatology (Oxford, England) 04/2015; 54(9). DOI:10.1093/rheumatology/kev032 · 4.48 Impact Factor

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14k Citations
3,372.49 Total Impact Points


  • 2008–2015
    • Friedrich-Alexander-University of Erlangen-Nürnberg
      • Nikolaus-Fiebiger-Center of Molecular Medicine (NFZ)
      Erlangen, Bavaria, Germany
  • 2007–2015
    • Universitätsklinikum Erlangen
      Erlangen, Bavaria, Germany
    • Universitätsklinikum Münster
      Muenster, North Rhine-Westphalia, Germany
  • 2012
    • University of British Columbia - Vancouver
      • Department of Psychology
      Vancouver, British Columbia, Canada
    • University of Amsterdam
      • Faculty of Medicine AMC
      Amsterdamo, North Holland, Netherlands
  • 2011
    • National Academy of Sciences of Ukraine
      • Institute of Cell Biology
      Kharkiv, Kharkivs'ka Oblast', Ukraine
    • University of Glasgow
      • College of Medical, Veterinary and Life Sciences
      Glasgow, Scotland, United Kingdom
  • 2008–2010
    • Nuremberg University of Music
      Nuremberg, Bavaria, Germany
  • 2009
    • University of Texas Southwestern Medical Center
      Dallas, Texas, United States
  • 1998–2008
    • Medical University of Vienna
      • Department of Medicine II
      Wien, Vienna, Austria
  • 2004–2006
    • Biomedical Sciences Research Center Alexander Fleming
      • Institute of Immunology
      Βάρη, Attica, Greece
  • 1998–2006
    • University of Vienna
      • Department of Internal Medicine III
      Wien, Vienna, Austria
  • 1995–2005
    • Austrian Academy of Sciences
      • • Research Center for Molecular Medicine
      • • Institut für Biomedizinische Alternsforschung
      Wien, Vienna, Austria
    • University of Innsbruck
      • Institute of Biochemistry
      Innsbruck, Tyrol, Austria
  • 2000
    • Vienna General Hospital
      Wien, Vienna, Austria