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Composition of TWIST1 dimers regulates fibroblast activation and tissue fibrosis
Conclusions Our data identify TWIST1 as a central pro-fibrotic factor in SSc, which facilitates fibroblast activation by amplifying TGFβ signalling. Targeting of TWIST1 may thus be a novel approach to normalise aberrant TGFβ signalling in SSc.
Source: Annals of the Rheumatic Diseases - December 8, 2016 Category: Rheumatology Authors: Palumbo-Zerr, K., Soare, A., Zerr, P., Liebl, A., Mancuso, R., Tomcik, M., Sumova, B., Dees, C., Chen, C.-W., Wohlfahrt, T., Mallano, T., Distler, A., Ramming, A., Gelse, K., Mihai, C., Distler, O., Schett, G., Distler, J. H. W. Tags: Immunology (including allergy), Connective tissue disease Basic and translational research Source Type: research

Methotrexate selectively targets human proinflammatory macrophages through a thymidylate synthase/p53 axis
Conclusions Macrophage response to MTX is polarisation-dependent and determined by the TS-p53 axis. CCL20 and LIF constitute novel macrophage markers for MTX responsiveness in vitro.
Source: Annals of the Rheumatic Diseases - November 9, 2016 Category: Rheumatology Authors: Municio, C., Soler Palacios, B., Estrada-Capetillo, L., Benguria, A., Dopazo, A., Garcia-Lorenzo, E., Fernandez-Arroyo, S., Joven, J., Miranda-Carus, M. E., Gonzalez-Alvaro, I., Puig-Kröger, A. Tags: Immunology (including allergy), Inflammation, Biological agents, Connective tissue disease, Degenerative joint disease, Drugs: musculoskeletal and joint diseases, Musculoskeletal syndromes, Rheumatoid arthritis Basic and translational research Source Type: research

Agrin mediates chondrocyte homeostasis and requires both LRP4 and {alpha}-dystroglycan to enhance cartilage formation in vitro and in vivo
Conclusions We have discovered that agrin strongly promotes chondrocyte differentiation and cartilage formation in vivo. Our results identify agrin as a novel potent anabolic growth factor with strong therapeutic potential in cartilage regeneration.
Source: Annals of the Rheumatic Diseases - May 9, 2016 Category: Rheumatology Authors: Eldridge, S., Nalesso, G., Ismail, H., Vicente-Greco, K., Kabouridis, P., Ramachandran, M., Niemeier, A., Herz, J., Pitzalis, C., Perretti, M., Dell'Accio, F. Tags: Open access, Immunology (including allergy), Degenerative joint disease, Musculoskeletal syndromes, Osteoarthritis Basic and translational research Source Type: research

Tribbles homologue 3 stimulates canonical TGF-{beta} signalling to regulate fibroblast activation and tissue fibrosis
Conclusions The present study characterises TRB3 as a novel profibrotic mediator in SSc. TGF-β induces TRB3, which in turn activates canonical TGF-β/Smad signalling and stimulates the release of collagen, thereby inducing a positive feedback loop that may contribute to aberrant TGF-β signalling in SSc.
Source: Annals of the Rheumatic Diseases - February 10, 2016 Category: Rheumatology Authors: Tomcik, M., Palumbo-Zerr, K., Zerr, P., Sumova, B., Avouac, J., Dees, C., Distler, A., Becvar, R., Distler, O., Schett, G., Senolt, L., Distler, J. H. W. Tags: Immunology (including allergy), Connective tissue disease Basic and translational research Source Type: research

The bromodomain protein inhibitor I-BET151 suppresses expression of inflammatory genes and matrix degrading enzymes in rheumatoid arthritis synovial fibroblasts
Conclusions Inhibition of BET family proteins suppresses the inflammatory, matrix-degrading, proliferative and chemoattractive properties of RASF and suggests a therapeutic potential in the targeting of epigenetic reader proteins in RA.
Source: Annals of the Rheumatic Diseases - January 11, 2016 Category: Rheumatology Authors: Klein, K., Kabala, P. A., Grabiec, A. M., Gay, R. E., Kolling, C., Lin, L.-L., Gay, S., Tak, P. P., Prinjha, R. K., Ospelt, C., Reedquist, K. A. Tags: Immunology (including allergy), Connective tissue disease, Degenerative joint disease, Musculoskeletal syndromes, Rheumatoid arthritis Basic and translational research Source Type: research

Inflammatory cytokines epigenetically regulate rheumatoid arthritis fibroblast-like synoviocyte activation by suppressing HDAC5 expression
Conclusions Inflammatory cytokines suppress RA FLS HDAC5 expression, promoting nuclear localisation of IRF1 and transcription of a subset of type I interferon response genes. Our results identify HDAC5 as a novel inflammatory mediator in RA, and suggest that strategies rescuing HDAC5 expression in vivo, or the development of HDAC inhibitors not affecting HDAC5 activity, may have therapeutic applications in RA treatment.
Source: Annals of the Rheumatic Diseases - January 11, 2016 Category: Rheumatology Authors: Angiolilli, C., Grabiec, A. M., Ferguson, B. S., Ospelt, C., Malvar Fernandez, B., van Es, I. E., van Baarsen, L. G. M., Gay, S., McKinsey, T. A., Tak, P. P., Baeten, D. L., Reedquist, K. A. Tags: Genetics, Immunology (including allergy), Connective tissue disease, Degenerative joint disease, Musculoskeletal syndromes, Rheumatoid arthritis Basic and translational research Source Type: research

Methotrexate-mediated activation of an AMPK-CREB-dependent pathway: a novel mechanism for vascular protection in chronic systemic inflammation
Conclusions These data suggest that MTX therapeutically conditions vascular endothelium via activation of AMPK-CREB. We propose that this mechanism contributes to the protection against cardiovascular events seen in patients with RA treated with MTX.
Source: Annals of the Rheumatic Diseases - January 11, 2016 Category: Rheumatology Authors: Thornton, C. C., Al-Rashed, F., Calay, D., Birdsey, G. M., Bauer, A., Mylroie, H., Morley, B. J., Randi, A. M., Haskard, D. O., Boyle, J. J., Mason, J. C. Tags: Open access, Genetics, Immunology (including allergy), Inflammation, Connective tissue disease, Degenerative joint disease, Musculoskeletal syndromes, Rheumatoid arthritis, Epidemiology Basic and translational research Source Type: research

A homeostatic function of CXCR2 signalling in articular cartilage
Conclusions Our study demonstrates an important physiological role for CXCR1/2 signalling in maintaining cartilage homeostasis and suggests that the loss of ELR+ CXC chemokines during cartilage breakdown in osteoarthritis contributes to the characteristic loss of chondrocyte phenotypic stability.
Source: Annals of the Rheumatic Diseases - November 10, 2015 Category: Rheumatology Authors: Sherwood, J., Bertrand, J., Nalesso, G., Poulet, B., Pitsillides, A., Brandolini, L., Karystinou, A., De Bari, C., Luyten, F. P., Pitzalis, C., Pap, T., Dell'Accio, F. Tags: Open access, Immunology (including allergy), Degenerative joint disease, Musculoskeletal syndromes, Osteoarthritis Basic and translational research Source Type: research

S100A4 amplifies TGF-{beta}-induced fibroblast activation in systemic sclerosis
Conclusions We characterised S100A4 as a downstream mediator of the stimulatory effects of TGF-β on fibroblasts in SSc. TGF-β induces the expression of S100A4 to stimulate the release of collagen in SSc fibroblasts and induce fibrosis. Since S100A4 is essentially required for the pro-fibrotic effects of TGF-β and neutralising antibodies against S100A4 are currently evaluated, S100A4 might be a candidate for novel antifibrotic therapies.
Source: Annals of the Rheumatic Diseases - August 10, 2015 Category: Rheumatology Authors: Tomcik, M., Palumbo-Zerr, K., Zerr, P., Avouac, J., Dees, C., Sumova, B., Distler, A., Beyer, C., Cerezo, L. A., Becvar, R., Distler, O., Grigorian, M., Schett, G., Senolt, L., Distler, J. H. W. Tags: Immunology (including allergy), Connective tissue disease Basic and translational research Source Type: research

Hypoxia and STAT3 signalling interactions regulate pro-inflammatory pathways in rheumatoid arthritis
Conclusions This is the first study to provide evidence of a functional link between HIF1α, STAT3 and Notch-1 signalling in the regulation of pro-inflammatory mechanisms in RA, and further supports a role for STAT blockade in the treatment of RA.
Source: Annals of the Rheumatic Diseases - May 8, 2015 Category: Rheumatology Authors: Gao, W., McCormick, J., Connolly, M., Balogh, E., Veale, D. J., Fearon, U. Tags: Immunology (including allergy), Connective tissue disease, Degenerative joint disease, Musculoskeletal syndromes, Rheumatoid arthritis Basic and translational research Source Type: research

Aryl hydrocarbon receptor antagonism mitigates cytokine-mediated inflammatory signalling in primary human fibroblast-like synoviocytes
Conclusions These data suggest that AHR antagonism may represent a viable adjuvant therapeutic strategy for the amelioration of inflammation associated with RA.
Source: Annals of the Rheumatic Diseases - September 4, 2013 Category: Rheumatology Authors: Lahoti, T. S., John, K., Hughes, J. M., Kusnadi, A., Murray, I. A., Krishnegowda, G., Amin, S., Perdew, G. H. Tags: Immunology (including allergy), Inflammation, Radiology, Connective tissue disease, Degenerative joint disease, Musculoskeletal syndromes, Rheumatoid arthritis, Clinical diagnostic tests, Epidemiology Basic and translational research Source Type: research

Nicotinamide phosphoribosyltransferase/visfatin expression by inflammatory monocytes mediates arthritis pathogenesis
Conclusions Our results show that the expression of NAMPT in Ly6Chigh monocytes promotes many downstream effects involved in inflammatory arthritis and demonstrate the utility of targeting disease-causing genes, such as NAMPT, in Ly6Chigh monocytes for therapeutic intervention in arthritis.
Source: Annals of the Rheumatic Diseases - September 4, 2013 Category: Rheumatology Authors: Presumey, J., Courties, G., Louis-Plence, P., Escriou, V., Scherman, D., Pers, Y.-M., Yssel, H., Pene, J., Kyburz, D., Gay, S., Jorgensen, C., Apparailly, F. Tags: Genetics, Immunology (including allergy), Connective tissue disease, Degenerative joint disease, Musculoskeletal syndromes, Rheumatoid arthritis Basic and translational research Source Type: research

Notch signalling pathways mediate synovial angiogenesis in response to vascular endothelial growth factor and angiopoietin 2
Conclusions Notch-1 mediates VEGF/Ang2-induced angiogenesis and EC invasion in inflammatory arthritis.
Source: Annals of the Rheumatic Diseases - May 10, 2013 Category: Rheumatology Authors: Gao, W., Sweeney, C., Walsh, C., Rooney, P., McCormick, J., Veale, D. J., Fearon, U. Tags: Open access, Immunology (including allergy), Pathology, Radiology, Degenerative joint disease, Musculoskeletal syndromes, Osteoarthritis, Surgical diagnostic tests, Clinical diagnostic tests Basic and translational research Source Type: research

Inhibition of H3K27 histone trimethylation activates fibroblasts and induces fibrosis
Conclusions These data demonstrate a novel role of H3 Lys27 histone methylation in fibrosis. In contrast to other epigenetic modifications such as DNA methylation and histone acetylation, H3 Lys27 histone methylation acts as a negative regulator of fibroblast activation in vitro and in vivo by repressing the expression of fra-2.
Source: Annals of the Rheumatic Diseases - February 25, 2013 Category: Rheumatology Authors: Kramer, M., Dees, C., Huang, J., Schlottmann, I., Palumbo-Zerr, K., Zerr, P., Gelse, K., Beyer, C., Distler, A., Marquez, V. E., Distler, O., Schett, G., Distler, J. H. W. Tags: Immunology (including allergy), Connective tissue disease Basic and translational research Source Type: research