Research Topics
Genomes and Genes
| Wim B van den BergSummaryAffiliation: Radboud University Nijmegen Medical Centre Country: The Netherlands Publications
| Collaborators
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Detail Information
Publications
Immunocytokines: the long awaited therapeutic magic bullet in rheumatoid arthritis?Fons A van de Loo
Rheumatology Research and Advanced Therapeutics, Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen 6525 GA, The Netherlands
Arthritis Res Ther 11:132. 2009..In principle, the scFv-targeting system is plastic enough to allow for personalized strategies...
Reduced transforming growth factor-beta signaling in cartilage of old mice: role in impaired repair capacityE N Blaney Davidson
Experimental Rheumatology and Advanced Therapeutics, St Radboud University Medical Centre Nijmegen, Geert Grooteplein 26, 6525 GA Nijmegen, The Netherlands
Arthritis Res Ther 7:R1338-47. 2005..In conclusion, TGF-beta appears to play an important role in repair of cartilage and a lack of TGF-beta responsiveness in old mice might be at the root of OA development...
Functional consequences of DECTIN-1 early stop codon polymorphism Y238X in rheumatoid arthritisTheo S Plantinga
Department of Medicine, Radboud University Nijmegen Medical Centre, P, O, Box 9101, 6500 HB Nijmegen, The Netherlands
Arthritis Res Ther 12:R26. 2010..In this study, dectin-1 mRNA and protein expression, as well as the recently characterized DECTIN-1 Y238X early stop codon polymorphism, were studied in relation to rheumatoid arthritis (RA) susceptibility and severity...
The human anti-IL-1 beta monoclonal antibody ACZ885 is effective in joint inflammation models in mice and in a proof-of-concept study in patients with rheumatoid arthritisRieke Alten
Department of Internal Medicine II, Rheumatology, Schlosspark Klinik Teaching Hospital Charité University Medicine Berlin, Heubnerweg, D 14059 Berlin, Germany
Arthritis Res Ther 10:R67. 2008..IL-1beta is a proinflammatory cytokine driving joint inflammation as well as systemic signs of inflammation, such as fever and acute phase protein production...
Elevated extracellular matrix production and degradation upon bone morphogenetic protein-2 (BMP-2) stimulation point toward a role for BMP-2 in cartilage repair and remodelingEsmeralda N Blaney Davidson
Experimental Rheumatology and Advanced Therapeutics, Radboud University Nijmegen Medical Centre, Geert Grooteplein 26 28, Nijmegen, 6500 HB, The Netherlands
Arthritis Res Ther 9:R102. 2007..Moreover, BMP contributes to the intrinsic repair capacity of damaged cartilage. Increased matrix turnover might be functional in replacing matrix molecules in the repair of a damaged cartilage matrix...
A role for age-related changes in TGFbeta signaling in aberrant chondrocyte differentiation and osteoarthritisPeter M van der Kraan
Experimental Rheumatology and Advanced Therapeutics, NCMLS, Radboud University, Medical Centre Nijmegen, Geert Grooteplein 28, 6525 GA Nijmegen, The Netherlands
Arthritis Res Ther 12:201. 2010..In this paper we summarize concepts in OA, its link with ageing and disturbed growth factor responses, and a potential role of TGFbeta signaling in OA development...
Animal models of arthritis. What have we learned?Wim B van den Berg
Rheumatology Research and Advanced Therapeutics Unit, University Medical Center St Radboud, 6500 HB Nijmegen, The Netherlands
J Rheumatol Suppl 72:7-9. 2005..Although in general more inflammation drives more destruction, the uncoupling of inflammation and erosion can be seen as well, and different mediators are involved in these processes...
Lessons from animal models of arthritis over the past decadeWim B van den Berg
Rheumatology Research and Advanced Therapeutics, Radboud University Nijmegen Medical Center, 6525 GA Nijmegen, The Netherlands
Arthritis Res Ther 11:250. 2009..Further insights into enzymes involved in cartilage proteoglycan loss in arthritis, as well as mediators regulating bone erosion and bone apposition, have been gained...
IL-17 as a future therapeutic target for rheumatoid arthritisWim B van den Berg
Rheumatology Research and Advanced Therapeutics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Nat Rev Rheumatol 5:549-53. 2009..The emergence of IL-17 blockade as a future therapy in rheumatoid arthritis is highlighted, along with the potential goals and limitations of this therapeutic approach...
Osteoarthritis year 2010 in review: pathomechanismsW B van den Berg
Rheumatology Research and Advanced Therapeutics, Radboud University Nijmegen Med Center RUNMC, The Netherlands
Osteoarthritis Cartilage 19:338-41. 2011..ALK-1 rather than TGF? is a promising therapeutic target. Finally, the alarmins S100A8 and 9 have long been considered as markers of inflammatory joint destruction, but now appear to be catabolic mediators...
Amplifying elements of arthritis and joint destructionWim B van den Berg
Rheumatology Research and Advanced Therapeutics, Radboud University Nijmegen Medical Center, Geert Grooteplein 26, 6525 GA Nijmegen, The Netherlands
Ann Rheum Dis 66:iii45-8. 2007..Spontaneous T cell-dependent arthritis in IL1Ra-/- mice is absent under germ-free conditions, and markedly suppressed in TLR4-deficient mice. Moreover, TLR4 blocking with a receptor antagonist suppresses erosive arthritis...
Trapped in a vicious loop: Toll-like receptors sustain the spontaneous cytokine production by rheumatoid synoviumShahla Abdollahi-Roodsaz
Rheumatology Research and Advanced Therapeutics, Department of Rheumatology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands
Arthritis Res Ther 13:105. 2011....
Lessons from animal models of osteoarthritisWim B van den Berg
Rheumatology Research and Advanced Therapeutics, Radboud University Nijmegen Medical Center, Geert Grooteplein 26, 6525 GA Nijmegen, The Netherlands
Curr Rheumatol Rep 10:26-9. 2008..Finally, transgenic mice show that osteoprotegerin is protective in OA, and treatment studies with recombinant osteoprotegerin have identified chondrocyte apoptosis blocking as an underlying mechanism...
Shift from toll-like receptor 2 (TLR-2) toward TLR-4 dependency in the erosive stage of chronic streptococcal cell wall arthritis coincident with TLR-4-mediated interleukin-17 productionShahla Abdollahi-Roodsaz
Rheumatology Research and Advanced Therapeutics, Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Arthritis Rheum 58:3753-64. 2008....
Fcgamma receptors directly mediate cartilage, but not bone, destruction in murine antigen-induced arthritis: uncoupling of cartilage damage from bone erosion and joint inflammationPeter L van Lent
Rheumatology Department, Radboud University Medical Centre, Nijmegen, The Netherlands
Arthritis Rheum 54:3868-77. 2006..To determine the relationship between synovial inflammation and the concomitant occurrence of cartilage and bone erosion during conditions of variable inflammation using various Fcgamma receptor knockout (FcgammaR(-/-)) mice...
T cell dependence of chronic destructive murine arthritis induced by repeated local activation of Toll-like receptor-driven pathways: crucial role of both interleukin-1beta and interleukin-17Leo A B Joosten
Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Arthritis Rheum 58:98-108. 2008..The present study was undertaken to develop a mouse model of chronic destructive arthritis induced by repeated intraarticular (IA) exposure to bacterial cell wall fragments and to investigate the cytokine dependence of this model...
Local IL-13 gene transfer prior to immune-complex arthritis inhibits chondrocyte death and matrix-metalloproteinase-mediated cartilage matrix degradation despite enhanced joint inflammationKarin C A M Nabbe
Department of Experimental Rheumatology and Advanced Therapeutics, University Medical Center Nijmegen, Nijmegen, The Netherlands
Arthritis Res Ther 7:R392-401. 2005..This study demonstrates that IL-13 overexpression during ICA diminished both chondrocyte death and MMP-mediated VDIPEN expression, even though joint inflammation was enhanced...
Interleukin-18 promotes joint inflammation and induces interleukin-1-driven cartilage destructionLeo A B Joosten
Rheumatology Research Laboratory and Advanced Therapeutics, University Medical Center Nijmegen, Nijmegen, The Netherlands
Am J Pathol 165:959-67. 2004..These findings implicate that IL-18, in contrast to TNF, contributes through separate pathways to joint inflammation and cartilage destruction...
The role of T-cell interleukin-17 in conducting destructive arthritis: lessons from animal modelsErik Lubberts
Department of Rheumatology, Rheumatology Research and Advanced Therapeutics, University Medical Center Nijmegen, Nijmegen, The Netherlands
Arthritis Res Ther 7:29-37. 2005..Anti-IL-17 cytokine therapy is of interest as an additional new anti-rheumatic strategy for RA, in particular in situations in which elevated IL-17 might attenuate the response to anti-TNF/anti-IL-1 therapy...
Interleukin-17 acts independently of TNF-alpha under arthritic conditionsMarije I Koenders
Experimental Rheumatology and Advanced Therapeutics, Radboud University Nijmegen Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlands
J Immunol 176:6262-9. 2006..These data provide further understanding of the cytokine interplay during inflammation and demonstrate that, despite a strong TNF dependency under naive conditions, IL-17 acts independently of TNF under arthritic conditions...
Interleukin-17 receptor deficiency results in impaired synovial expression of interleukin-1 and matrix metalloproteinases 3, 9, and 13 and prevents cartilage destruction during chronic reactivated streptococcal cell wall-induced arthritisMarije I Koenders
University Medical Center St. Radboud, Nijmegen, The Netherlands
Arthritis Rheum 52:3239-47. 2005..Prevention of IL-17R signaling warrants consideration as a therapeutic target in chronic destructive arthritis...
TLR2 promotes Th2/Th17 responses via TLR4 and TLR7/8 by abrogating the type I IFN amplification loopMark H Wenink
Department of Rheumatology, Radboud University Nijmegen Medical Center, Geert Grooteplein 8, 6500 HB Nijmegen, The Netherlands
J Immunol 183:6960-70. 2009..This shift in T cell responses was inherent to the inability of TLR2-stimulated DCs to produce IL-12p70 and was dependent on the production of IL-1 and IL-6...
Blocking of interleukin-17 during reactivation of experimental arthritis prevents joint inflammation and bone erosion by decreasing RANKL and interleukin-1Marije I Koenders
Department of Rheumatology, Experimental Rheumatology and Advanced Therapeutics, Radboud University Nijmegen Medical Center, 189, Geert Grooteplein Zuid 26 28, PO Box 9101, 6500 HB Nijmegen, The Netherlands
Am J Pathol 167:141-9. 2005..These data indicate that IL-17 is an important upstream mediator in joint pathology during flare-up of experimental arthritis...
Toll-like receptor 2 pathway drives streptococcal cell wall-induced joint inflammation: critical role of myeloid differentiation factor 88Leo A B Joosten
Rheumatology Research Laboratory and Advanced Therapeutics, University Medical Center Nijmegen, Nijmegen, The Netherlands
J Immunol 171:6145-53. 2003..Since agonists of the Toll-like pathway are abundantly involved in both septic and rheumatoid arthritis, targeting of MyD88 may be a novel therapy in inflammatory joint diseases...
Treatment with a neutralizing anti-murine interleukin-17 antibody after the onset of collagen-induced arthritis reduces joint inflammation, cartilage destruction, and bone erosionErik Lubberts
University Medical Center Nijmegen, Nijmegen, The Netherlands
Arthritis Rheum 50:650-9. 2004..Our data strongly indicate that IL-17 neutralization could provide an additional therapeutic strategy for RA, particularly in situations in which elevated IL-17 may attenuate the response to anti-tumor necrosis factor/anti-IL-1 therapy...
IL-17 promotes bone erosion in murine collagen-induced arthritis through loss of the receptor activator of NF-kappa B ligand/osteoprotegerin balanceErik Lubberts
Rheumatology and Advanced Therapeutics, University Medical Center Nijmegen, Nijmegen, The Netherlands
J Immunol 170:2655-62. 2003..These findings suggest T cell IL-17 to be an important inducer of RANKL expression leading to loss of the RANKL/OPG balance, stimulating osteoclastogenesis and bone erosion in arthritis...
IL-32gamma and Streptococcus pyogenes cell wall fragments synergise for IL-1-dependent destructive arthritis via upregulation of TLR-2 and NOD2Bas Heinhuis
Rheumatology Research and Advanced Therapeutics, Department of Rheumatology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500HB, Nijmegen, The Netherlands
Ann Rheum Dis 69:1866-72. 2010..To investigate the potential synergism between interleukin (IL) 32? and Streptococcus pyogenes cell wall (SCW) fragments in the development of destructive arthritis...
A crucial role for tumor necrosis factor receptor 1 in synovial lining cells and the reticuloendothelial system in mediating experimental arthritisOnno J Arntz
Rheumatology Research and Advanced Therapeutics, Department of Rheumatology, Radboud University Nijmegen Medical Centre, 6525 GA Nijmegen, The Netherlands
Arthritis Res Ther 12:R61. 2010..The objective is to investigate the role of TNFR1 in the synovial lining cells (SLC) and the reticuloendothelial system (RES) during experimental arthritis...
Involvement of the Wnt signaling pathway in experimental and human osteoarthritis: prominent role of Wnt-induced signaling protein 1Arjen B Blom
Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Arthritis Rheum 60:501-12. 2009..The present study was undertaken to characterize the expression pattern of Wnt and Fz genes during experimental OA and to determine the function of selected genes in experimental and human OA...
Local activation of STAT-1 and STAT-3 in the inflamed synovium during zymosan-induced arthritis: exacerbation of joint inflammation in STAT-1 gene-knockout miceAlfons S K de Hooge
University Medical Center Nijmegen, Nijmegen, The Netherlands
Arthritis Rheum 50:2014-23. 2004..The present study was undertaken to investigate synovial STAT-1 and STAT-3 activation in an experimental animal model of arthritis...
Expression of toll-like receptors 2 and 4 in rheumatoid synovial tissue and regulation by proinflammatory cytokines interleukin-12 and interleukin-18 via interferon-gammaTimothy R D J Radstake
University Medical Center Nijmegen, Nijmegen, The Netherlands
Arthritis Rheum 50:3856-65. 2004..The synergistic effect of IL-12 and IL-18 on T cell IFNgamma production seems to regulate expression of TLR-2 and TLR-4 in the synovial tissue of RA patients...
Inflammatory arthritis in caspase 1 gene-deficient mice: contribution of proteinase 3 to caspase 1-independent production of bioactive interleukin-1betaLeo A B Joosten
Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Arthritis Rheum 60:3651-62. 2009..This study was undertaken to establish the relative importance of caspase 1 and serine proteases in mouse models of acute and chronic inflammatory arthritis...
Intravenously delivered glucocorticoid liposomes inhibit osteoclast activity and bone erosion in murine antigen-induced arthritisWouter Hofkens
Rheumatology Research and Advanced Therapeutics, Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
J Control Release 152:363-9. 2011..Conclusion: Liposomal glucocorticoid delivery rather than free PLP offers a more efficacious way to inhibit both inflammation and bone erosion in rheumatoid arthritis...
Deficiency of NADPH oxidase components p47phox and gp91phox caused granulomatous synovitis and increased connective tissue destruction in experimental arthritis modelsFons A J van de Loo
Department of Rheumatology, University Medical Center Nijmegen, Nijmegen, The Netherlands
Am J Pathol 163:1525-37. 2003..This showed that the involvement of NADPH oxidase in arthritis is probably far more complex and that oxygen radicals might also be important in controlling disease severity, and reducing joint inflammation and connective tissue damage...
FcgammaRI up-regulation induced by local adenoviral-mediated interferon-gamma production aggravates chondrocyte death during immune complex-mediated arthritisKarin C Nabbe
Department of Experimental Rheumatology and Advanced Therapeutics, University Medical Center, Nijmegen, The Netherlands
Am J Pathol 163:743-52. 2003..These results indicate that IFN-gamma overexpression deteriorates cartilage destruction in the presence of ICs and that FcgammaRI is crucial in the development of chondrocyte death...
NADPH-oxidase-driven oxygen radical production determines chondrocyte death and partly regulates metalloproteinase-mediated cartilage matrix degradation during interferon-gamma-stimulated immune complex arthritisPeter L E M van Lent
Department of Rheumatology, University Medical Centre, St Radboud, Nijmegen, The Netherlands
Arthritis Res Ther 7:R885-95. 2005..Upregulation of FcgammaRI by oxygen radicals may contribute to cartilage destruction...
Different amplifying mechanisms of interleukin-17 and interferon-gamma in Fcgamma receptor-mediated cartilage destruction in murine immune complex-mediated arthritisLilyanne C Grevers
Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Arthritis Rheum 60:396-407. 2009..This study was undertaken to determine the role of IL-17 in FcgammaR-mediated cartilage destruction in IC-mediated arthritis and to compare its effect with that of IFNgamma...
The functional variant of the inhibitory Fcgamma receptor IIb (CD32B) is associated with the rate of radiologic joint damage and dendritic cell function in rheumatoid arthritisTimothy R D J Radstake
Department of Rheumatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Arthritis Rheum 54:3828-37. 2006..The purpose of this study was to unravel the role of the inhibitory FcgammaRIIb in rheumatoid arthritis (RA) by studying the effect of the FCGR2B 695T>C polymorphism on susceptibility to RA, severity of the disease, and DC function...
Inflammation-dependent secretion and splicing of IL-32{gamma} in rheumatoid arthritisBas Heinhuis
Rheumatology Research and Advanced Therapeutics, Department of Rheumatology, Radboud University Nijmegen Medical Centre, 6500 HB, Nijmegen, The Netherlands
Proc Natl Acad Sci U S A 108:4962-7. 2011..Splicing of IL-32? into IL-32? is a safety switch in controlling the effects of IL-32? and thereby reduces chronic inflammation...
S100A8 causes a shift toward expression of activatory Fc? receptors on macrophages via toll-like receptor 4 and regulates Fc? receptor expression in synovium during chronic experimental arthritisPeter L van Lent
Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Arthritis Rheum 62:3353-64. 2010..This study was undertaken to study the active involvement of S100A8, S100A9, and S100A8/S100A9 in Fc?R regulation in murine macrophages and synovium during AIA...
Interleukin-1 drives pathogenic Th17 cells during spontaneous arthritis in interleukin-1 receptor antagonist-deficient miceMarije I Koenders
Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Arthritis Rheum 58:3461-70. 2008..In this study, the role of Th17 cells and the effect of neutralization of IL-17, IL-1, and tumor necrosis factor alpha (TNFalpha) were investigated in this IL-1-driven murine arthritis model...
S100A8 enhances osteoclastic bone resorption in vitro through activation of Toll-like receptor 4: implications for bone destruction in murine antigen-induced arthritisLilyanne C Grevers
Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Arthritis Rheum 63:1365-75. 2011..The aim of the present study was to investigate the role of S100A8 and S100A9 in osteoclastic bone destruction in murine antigen-induced arthritis (AIA)...
Crucial role of macrophages in matrix metalloproteinase-mediated cartilage destruction during experimental osteoarthritis: involvement of matrix metalloproteinase 3Arjen B Blom
Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands
Arthritis Rheum 56:147-57. 2007..To explore the involvement of synovial macrophages in early cartilage damage in osteoarthritis (OA), and to identify the role of matrix metalloproteinase 3 (MMP-3) in the pathology of early and late OA...
IL-32, a proinflammatory cytokine in rheumatoid arthritisLeo A B Joosten
Rheumatology Research and Advanced Therapeutics, Radboud University Nijmegen Medical Centre, The Netherlands
Proc Natl Acad Sci U S A 103:3298-303. 2006..IL-32, strongly associated with TNFalpha, IL-1beta, and IL-18, appears to play a role in human RA and may be a novel target in autoimmune diseases...
Local interleukin-1-driven joint pathology is dependent on toll-like receptor 4 activationShahla Abdollahi-Roodsaz
Department of Rheumatology, Radboud University Nijmegen Medical Centre, The Netherlands
Am J Pathol 175:2004-13. 2009..These data emphasize the potential relevance of TLR4 activation in rheumatoid arthritis, particularly with respect to IL-1-mediated joint pathology...
The functional variant (Asp299gly) of toll-like receptor 4 (TLR4) influences TLR4-mediated cytokine production in rheumatoid arthritisMieke F Roelofs
Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
J Rheumatol 35:558-61. 2008..To investigate functional consequences of the Toll-like receptor 4 (TLR4) variant (Asp299Gly) in rheumatoid arthritis (RA)...
Splenic suppressor of cytokine signaling 3 transgene expression affects T cell responses and prevents development of collagen-induced arthritisSharon Veenbergen
Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Arthritis Rheum 58:3742-52. 2008....
The inhibitory Fc gamma IIb receptor dampens TLR4-mediated immune responses and is selectively up-regulated on dendritic cells from rheumatoid arthritis patients with quiescent diseaseMark H Wenink
Department of Rheumatology, Nijmegen Centre of Molecular Life Sciences and Radboud University Nijmegen Medical Centre, Geert Grooteplein 8, Nijmegen 6500 HB, The Netherlands
J Immunol 183:4509-20. 2009..This TLR4-FcgammaRIIb interaction was shown to dependent on the PI3K and Akt pathway...
Increase in ALK1/ALK5 ratio as a cause for elevated MMP-13 expression in osteoarthritis in humans and miceEsmeralda N Blaney Davidson
Rheumatology Research and Advanced Therapeutics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
J Immunol 182:7937-45. 2009..Our data suggest that dominant ALK1 signaling results in deviant chondrocyte behavior, thereby contributing to age-related cartilage destruction and OA...
Stimulation of TLR2 and TLR4 differentially skews the balance of T cells in a mouse model of arthritisShahla Abdollahi-Roodsaz
Rheumatology Research and Advanced Therapeutics, Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
J Clin Invest 118:205-16. 2008....
Computational design and application of endogenous promoters for transcriptionally targeted gene therapy for rheumatoid arthritisJeroen Geurts
Rheumatology Research and Advanced Therapeutics, Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Mol Ther 17:1877-87. 2009..These results demonstrate the value of bioinformatics for guiding the selection of endogenous promoters for transcriptionally targeted gene therapy...
The molecular signature of oxidative metabolism and the mode of macrophage activation determine the shift from acute to chronic disease in experimental arthritis: critical role of interleukin-12p40Nozomi Takahashi
Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Arthritis Rheum 58:3471-84. 2008..The objective of this study was to identify genes and pathways that determine disease progression based on gene expression profiling in this model...
Inhibition of Toll-like receptor 4 breaks the inflammatory loop in autoimmune destructive arthritisShahla Abdollahi-Roodsaz
Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Arthritis Rheum 56:2957-67. 2007..The objective of this study was to investigate the involvement of TLR-4 activation in the development and progression of autoimmune destructive arthritis...
Male IL-6 gene knock out mice developed more advanced osteoarthritis upon agingAlfons S K de Hooge
Rheumatology Research Laboratory, University Medical Center Nijmegen, Nijmegen Center for Molecular Life Sciences, Nijmegen, The Netherlands
Osteoarthritis Cartilage 13:66-73. 2005..Interleukin-6 (IL-6) is expressed in osteoarthritic joints but its function in osteoarthritis (OA) is unknown. To study this, spontaneous and experimental OA were evaluated in IL-6 deficient (IL-6(-/-)) mice...
Induction of cartilage damage by overexpression of T cell interleukin-17A in experimental arthritis in mice deficient in interleukin-1Marije I Koenders
University Medical Center St Radboud, Nijmegen, The Netherlands
Arthritis Rheum 52:975-83. 2005..To examine the capacity of T cell interleukin-17A (IL-17A; referred to hereinafter as IL-17) to induce cartilage damage during experimental arthritis in the absence of IL-1...
Growth plate damage, a feature of juvenile idiopathic arthritis, can be induced by adenoviral gene transfer of oncostatin M: a comparative study in gene-deficient miceAlfons S K de Hooge
Rheumatology Research Laboratory, University Medical Center Nijmegen, Nijmegen Center for Molecular Life Sciences, Nijmegen, The Netherlands
Arthritis Rheum 48:1750-61. 2003..The effect of OSM on murine connective tissue and the presence of OSM in human synovial fluid make involvement of OSM in human arthropathies very likely...
A pivotal role for antigen-presenting cells overexpressing SOCS3 in controlling invariant NKT cell responses during collagen-induced arthritisSharon Veenbergen
Correspondence to F A J van de Loo, Rheumatology Research and Advanced Therapeutics, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Molecular Life Sciences, Geert Grooteplein 26 28, 6500 HB Nijmegen, The Netherlands
Ann Rheum Dis 70:2167-75. 2011..A study was undertaken to investigate the contribution of SOCS3 in regulating invariant natural killer T (iNKT) cell responses during collagen-induced arthritis (CIA)...
Reduction of osteophyte formation and synovial thickening by adenoviral overexpression of transforming growth factor beta/bone morphogenetic protein inhibitors during experimental osteoarthritisAlwin Scharstuhl
University Medical Center Nijmegen, Nijmegen, The Netherlands
Arthritis Rheum 48:3442-51. 2003..This is the first study to demonstrate that endogenous BMPs are involved in osteophyte formation and synovial thickening in experimental OA...
Tumour necrosis factor alpha-driven IL-32 expression in rheumatoid arthritis synovial tissue amplifies an inflammatory cascadeBas Heinhuis
Rheumatology Research and Advanced Therapeutics, Department of Rheumatology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500HB, Nijmegen, The Netherlands
Ann Rheum Dis 70:660-7. 2011..To investigate the interplay between IL-32 and tumour necrosis factor alpha (TNF?) during the chronic inflammation of rheumatoid arthritis (RA) and to assess whether anti-TNF? treatment of RA patients modulates synovial IL-32 expression...
Inhibition of endogenous TGF-beta during experimental osteoarthritis prevents osteophyte formation and impairs cartilage repairAlwin Scharstuhl
Rheumatology Research Laboratory, Department of Rheumatology, University Medical Center, Nijmegen, The Netherlands
J Immunol 169:507-14. 2002..In conclusion, we show for the first time that endogenous TGF-beta is a crucial factor in the process of osteophyte formation and has an important function in protection against cartilage loss...
Interleukin 32 (IL-32) contains a typical ?-helix bundle structure that resembles focal adhesion targeting region of focal adhesion kinase-1Bas Heinhuis
Rheumatology Research and Advanced Therapeutics, Department of Rheumatology, Radboud University Nijmegen Medical Centre, 6500 HB, Nijmegen, The Netherlands
J Biol Chem 287:5733-43. 2012..This study demonstrates for the first time that IL-32 binds to the extracellular domain of integrins and to intracellular proteins like paxillin and FAK, suggesting a dual role for IL-32 in integrin signaling...
TGF beta-induced cartilage repair is maintained but fibrosis is blocked in the presence of Smad7Esmeralda N Blaney Davidson
Experimental Rheumatology and Advanced Therapeutics, St, Radboud University Medical Centre Nijmegen, Geert Grooteplein 26 28, 6525 GA Nijmegen, The Netherlands
Arthritis Res Ther 8:R65. 2006..TGFbeta-induced synovial fibrosis was blocked by locally inhibiting TGFbeta signaling in the synovial lining by simultaneously transfecting it with an adenovirus overexpressing Smad7...
Large scale protein production of the extracellular domain of the transforming growth factor-beta type II receptor using the Pichia pastoris expression systemAlwin Scharstuhl
Rheumatology Research Laboratory, Department of Rheumatology, University Medical Center Nijmegen, Geert Grooteplein Zuid 26 28, 6525 GA, Nijmegen, The Netherlands
J Chromatogr B Analyt Technol Biomed Life Sci 786:271-7. 2003..In conclusion, our large-scale protein expression procedure results in high quantities of purified solRII, which is a powerful tool to study the natural role of TGF-beta...
IL-17 produced by Paneth cells drives TNF-induced shockNozomi Takahashi
Rheumatology Research and Advanced Therapeutics, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, Netherlands
J Exp Med 205:1755-61. 2008..These data indicate that innate immune cytokine responses in the local mucosa may participate in rapidly amplifying responses to systemic inflammatory challenges...
Tumor necrosis factor-interleukin-17 interplay induces S100A8, interleukin-1?, and matrix metalloproteinases, and drives irreversible cartilage destruction in murine arthritis: rationale for combination treatment during arthritisMarije I Koenders
Radboud University Nijmegen Medical Centre, Department of Rheumatology, Nijmegen, The Netherlands
Arthritis Rheum 63:2329-39. 2011....
Safety of glucocorticoids can be improved by lower yet still effective dosages of liposomal steroid formulations in murine antigen-induced arthritis: comparison of prednisolone with budesonideWouter Hofkens
Rheumatology Research and Advanced Therapeutics, Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Int J Pharm 416:493-8. 2011..Conclusion: Liposomal delivery improves the safety of glucocorticoids by allowing for lower effective dosing. The safety of liposomal glucocorticoid may be further improved by encapsulating BUP rather than PLP...
Citrullination of synovial proteins in murine models of rheumatoid arthritisErik R Vossenaar
Department of Biochemistry, University of Nijmegen, Nijmegen, The Netherlands
Arthritis Rheum 48:2489-500. 2003....
Differential function of the NACHT-LRR (NLR) members Nod1 and Nod2 in arthritisLeo A B Joosten
Rheumatology Research and Advanced Therapeutics, Department of Rheumatology, Radboud University Nijmegen Medical Centre, P O Box 9101, 6500 HB, Nijmegen, The Netherlands
Proc Natl Acad Sci U S A 105:9017-22. 2008..Whether a distorted balance between the function of Nod1 and/or Nod2 is involved in the pathogenesis of human autoinflammatory or autoimmune disease, such as rheumatoid arthritis, remains to be elucidated...
Increased expression of Fcgamma receptors II and III on macrophages of rheumatoid arthritis patients results in higher production of tumor necrosis factor alpha and matrix metalloproteinaseArjen B Blom
University Medical Center, Nijmegen, The Netherlands
Arthritis Rheum 48:1002-14. 2003..These data suggest that disturbed expression of FcgammaR on mature synovial macrophages is involved in the pathology of RA...
The anti-CD20 antibody rituximab reduces the Th17 cell responseFrank L van de Veerdonk
Radboud University Nijmegen Medical Center and Nijmegen Institute for Infection, Inflammation, and Immunity, Nijmegen, The Netherlands
Arthritis Rheum 63:1507-16. 2011..The present study was undertaken to investigate the mechanism of action of rituximab in RA...
A novel Saa3-promoter reporter distinguishes inflammatory subtypes in experimental arthritis and human synovial fibroblastsJeroen Geurts
Rheumatology Research and Advanced Therapeutics, Department of Rheumatology, Radboud University Nijmegen Medical Centre, The Netherlands
Ann Rheum Dis 70:1311-9. 2011....
Association of interleukin-18 expression with enhanced levels of both interleukin-1beta and tumor necrosis factor alpha in knee synovial tissue of patients with rheumatoid arthritisLeo A B Joosten
Rheumatology Research Laboratory, University Medical Center Nijmegen, Nijmegen, The Netherlands
Arthritis Rheum 48:339-47. 2003....
Increase in expression of receptor activator of nuclear factor kappaB at sites of bone erosion correlates with progression of inflammation in evolving collagen-induced arthritisErik Lubberts
University Medical Center Nijmegen, Nijmegen, The Netherlands
Arthritis Rheum 46:3055-64. 2002..This study was undertaken to identify in vivo the hitherto-unknown origin and localization of RANK-expressing osteoclast precursor cells at sites of bone erosion in arthritis...
Expression of the dendritic cell-associated C-type lectin DC-SIGN by inflammatory matrix metalloproteinase-producing macrophages in rheumatoid arthritis synovium and interaction with intercellular adhesion molecule 3-positive T cellsPeter L E M van Lent
Department of Rheumatology, University Medical Centre Nijmegen, Nijmegen, The Netherlands
Arthritis Rheum 48:360-9. 2003....
Local interleukin-12 gene transfer promotes conversion of an acute arthritis to a chronic destructive arthritisLeo A B Joosten
Rheumatology Research Laboratory, University Medical Center Nijmegen, Nijmegen, The Netherlands
Arthritis Rheum 46:1379-89. 2002....
Elevated CXCL16 expression by synovial macrophages recruits memory T cells into rheumatoid jointsRobbert van der Voort
Nijmegen Center for Molecular Life Sciences, University Medical Center St. Radboud, Nijmegen, The Netherlands
Arthritis Rheum 52:1381-91. 2005..CONCLUSION: These data provide evidence that enhanced production of CXCL16 in RA synovia leads to recruitment of CXCR6+ memory T cells, thereby contributing to the inflammatory cascade associated with RA pathology...
Differential role of IL-18 and IL-12 in the host defense against disseminated Candida albicans infectionMihai G Netea
Department of Medicine, University Medical Center St. Radboud, Nijmegen, Nijmegen, The Netherlands
Eur J Immunol 33:3409-17. 2003..In conclusion, the anticandidal effects of endogenous IL-18 are mediated late during the infection by assuring a proper IFN-gamma response and promoting the infiltration of the site of infection by monocytes...
The Toll-like receptor 4 Asp299Gly functional variant is associated with decreased rheumatoid arthritis disease susceptibility but does not influence disease severity and/or outcomeTimothy R D J Radstake
University Medical Center Nijmegen, Nijmegen, The Netherlands
Arthritis Rheum 50:999-1001. 2004
The macrophage mannose receptor induces IL-17 in response to Candida albicansFrank L van de Veerdonk
Department of Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Cell Host Microbe 5:329-40. 2009..This study identifies the specific pattern recognition receptors that trigger the Th17 response induced by a human pathogen in the absence of mitogenic stimulation...
Osteoarthritis in the context of ageing and evolution. Loss of chondrocyte differentiation block during ageingPeter M van der Kraan
Experimental Rheumatology and Advanced Therapeutics, NCMLS, Radboud University, Medical Centre, Geert Grooteplein 28, Nijmegen, The Netherlands
Ageing Res Rev 7:106-13. 2008..The loss of this differentiation block, maybe as a result of changes in chondrocyte TGF beta signalling, results in combination with normal joint loading in cartilage degeneration and OA...
Increased expression of interleukin-22 by synovial Th17 cells during late stages of murine experimental arthritis is controlled by interleukin-1 and enhances bone degradationRenoud J Marijnissen
Radboud University Nijmegen Medical Centre, Department of Rheumatology, Rheumatology Research and Advanced Therapeutics, Nijmegen, The Netherlands
Arthritis Rheum 63:2939-48. 2011....
Toll-like receptor 4 signalling is specifically TGF-beta-activated kinase 1 independent in synovial fibroblastsJeroen Geurts
Department of Rheumatology, Rheumatology Research and Advanced Therapeutics, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands
Rheumatology (Oxford) 50:1216-25. 2011..In this study, we sought to determine the role of the MAP3K TGF-?-activated kinase 1 (TAK1) in cytokine and TLR-mediated signalling...
Cytokine targeting in osteoarthritisArjen B Blom
Experimental Rheumatology and Advanced Therapeutics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Curr Drug Targets 8:283-92. 2007..g. with or without marked synovial activation, treatment may be focused mainly on suppression of catabolism or stimulation of anabolism, but combination therapy seems most warranted...
Osteophytes: relevance and biologyPeter M van der Kraan
Experimental Rheumatology and Advanced Therapeutics, NCMLS, Radboud University, Medical Center Nijmegen, The Netherlands
Osteoarthritis Cartilage 15:237-44. 2007..Osteophytes are common features of osteoarthritis. This review summarizes the current understanding of the clinical relevance and biology of osteophytes...
Cytokines and joint erosion in arthritisWim B van den Berg
Rheumatology Research and Advanced Therapeutics, Radboud University, Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlandsw
Nat Clin Pract Rheumatol 4:58-9. 2008
Gene therapy works in animal models of rheumatoid arthritis...so what!Fons A J van de Loo
Rheumatology Research and Advanced Therapeutics, Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Molecular Life Sciences, Geert Grooteplein 28, 6525 GA Nijmegen, The Netherlands
Curr Rheumatol Rep 8:386-93. 2006....
Cross-linked type I and type II collagenous matrices for the repair of full-thickness articular cartilage defects--a study in rabbitsPieter Buma
Orthopedic Research Laboratory, Department of Orthopedics, University Medical Center Nijmegen, P O Box 9101, The Netherlands
Biomaterials 24:3255-63. 2003..Based on these observations it is suggested that a composite matrix consisting of a deep layer of type I collagen and a more superficial layer of type II collagen may be the matrix of choice for cartilage regeneration...
Selectively induced death of macrophages in the synovial lining of murine knee joints using 10B-liposomes and boron neutron capture synovectomyPeter L E M van Lent
Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Int J Radiat Biol 85:860-71. 2009....
Tumor marker nucleoporin 88 kDa regulates nucleocytoplasmic transport of NF-kappaBNozomi Takahashi
Rheumatology Research and Advanced Therapeutics, 272, NCMLS, Radboud University Medical Centre Nijmegen, P O Box 9101, Geert Grooteplein 26 28, 6500 HB Nijmegen, The Netherlands
Biochem Biophys Res Commun 374:424-30. 2008..We conclude that Nup88 regulates the activity of NF-kappaB at the level of nucleocytoplasmic transport. Overexpression of Nup88 in tumor cells may, thus be involved in the constitutive NF-kappaB activation...
Identification of small heat shock protein B8 (HSP22) as a novel TLR4 ligand and potential involvement in the pathogenesis of rheumatoid arthritisMieke F Roelofs
Department of Rheumatology Research and Advanced Therapeutics, Nijmegen Center for Molecular Life Sciences, The Netherlands
J Immunol 176:7021-7. 2006..These findings suggest a role for HSPB8 during the inflammatory process in autoimmune diseases such as RA...
Role of gene therapy in tissue engineering procedures in rheumatology: the use of animal modelsPeter M van der Kraan
Experimental Rheumatology and Advanced Therapeutics, Nijmegen Center for Molecular Life Sciences, University Medical Center Nijmegen, Geert Grooteplein 26 28, GA 6525, Nijmegen, The Netherlands
Biomaterials 25:1497-504. 2004..Development of animal models that can be used for tissue engineering experiments and mimic end stage arthritic diseases is needed...
Synovial lining macrophages mediate osteophyte formation during experimental osteoarthritisArjen B Blom
Experimental Arthritis and Advanced Therapies, University Medical Center Nijmegen, The Netherlands
Osteoarthritis Cartilage 12:627-35. 2004..The objective of this study was to investigate whether synovial macrophages are involved in osteophyte formation in experimental OA, and if they are, to study which mechanism may be involved...
Requirement of IL-17 receptor signaling in radiation-resistant cells in the joint for full progression of destructive synovitisErik Lubberts
Department of Medicine, Gene Therapy Program, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
J Immunol 175:3360-8. 2005..These data strongly indicate that IL-17R signaling in radiation-resistant cells in the joint is required for turning an acute macrophage-mediated inflammation into a chronic destructive synovitis...
Uncoupling of inflammation and destruction in rheumatoid arthritis: myth or reality?Wim B van den Berg
Arthritis Rheum 52:995-9. 2005
Destructive arthritis in the absence of both FcgammaRI and FcgammaRIIIPeter Boross
Department of Human Genetics, Leiden University Medical Center, Leiden
J Immunol 180:5083-91. 2008..In addition, FcgammaRII plays a negative regulatory role in both the central and effector phase of arthritis...
Influence of heme oxygenase 1 modulation on the progression of murine collagen-induced arthritisIsabel Devesa
University of Valencia, Burjassot, Valencia, Spain
Arthritis Rheum 52:3230-8. 2005....
Decreased pro-inflammatory cytokine production by LPS-stimulated PBMC upon in vitro incubation with the flavonoids apigenin, luteolin or chrysin, due to selective elimination of monocytes/macrophagesSander Hougee
Numico Research, P O Box 7005, Wageningen 6700, The Netherlands
Biochem Pharmacol 69:241-8. 2005..In conclusion, monocytes were specifically eliminated in PBMC by apigenin, chrysin or luteolin treatment in vitro at low concentrations (around 8 microM), in which apigenin appeared to be the most potent...
Gene therapy for rheumatoid arthritis. Lessons from animal models, including studies on interleukin-4, interleukin-10, and interleukin-1 receptor antagonist as potential disease modulatorsFons A J van de Loo
Department of Rheumatology, University Medical Center Nijmegen, Nijmegen, The Netherlands
Rheum Dis Clin North Am 28:127-49. 2002..The feasibility of viral transduction of chondrocytes to obtain a tissue-specific approach to treat articular cartilage damage in arthritis needs further attention...
Gene therapy in animal models of rheumatoid arthritis: are we ready for the patients?Fons A J van de Loo
Rheumatology Research and Advanced Therapeutics, Department of Rheumatology, University Medical Center Nijmegen, Nijmegen Center for Molecular Life Sciences, Nijmegen, The Netherlands
Arthritis Res Ther 6:183-96. 2004..Evidence from animal models convincingly supports the application of gene therapy in RA, and the feasibility of gene therapy was recently demonstrated in phase I clinical trials...
Anticytokine treatment of established type II collagen-induced arthritis in DBA/1 mice: a comparative study using anti-TNFalpha, anti-IL-1alpha/beta and IL-1RaLeo A B Joosten
University Hospital Nijimegen, Nijimegen, The Netherlands
Arthritis Rheum 58:S110-22. 2008..To examine the role of tumor necrosis factor alpha (TNF alpha), interleukin-1 alpha (IL-1 alpha), and IL-1 beta in collagen-induced arthritis (CIA), immediately after onset and during the phase of established arthritis...
Oral administration of the NADPH-oxidase inhibitor apocynin partially restores diminished cartilage proteoglycan synthesis and reduces inflammation in miceSander Hougee
Numico Research P O Box 7005, Wageningen, NL 6700 CA Wageningen, The Netherlands
Eur J Pharmacol 531:264-9. 2006..Therefore, apocynin might be of potential use during the treatment of chronic inflammatory joint diseases like osteoarthritis or rheumatoid arthritis...
