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Hill CL, Hunter DJ, Niu J, et al. Synovitis detected on magnetic resonance imaging and its relation to pain and cartilage loss in knee osteoarthritis. Ann Rheum Dis 2007; 66:1599-1603. This imaging study of close to 300 patients with knee osteoarthritis documents a relationship between changes in synovitis and pain scores in a longitudinal manner. This report follows up this group's original cross-sectional analysis published in 2001, which was one of the first to demonstrate an association of synovial changes (seen on imaging) with symptoms in osteoarthritis patients.
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Roelofs MF, Abdollahi-Roodsaz S, Joosten LA, et al. The orchestra of Toll-like receptors and their potential role in frequently occurring rheumatic conditions. Arthritis Rheum 2008; 58:338-348. Thisisa very recent in-depth synthesis of the available data on TLR signalingin driving RA, seronegative spondyloarthropathies, and systemic lupus erythamatosis. Although there may be substantial differences in the pattern of activation and downstream effects of TLR pathways in osteoarthritis compared with these rheumatic conditions, the information contained herein is relevant to the future study of these pathways in joint tissues from other disorders.
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Kaczorowski DJ, Mollen KP, Edmonds R, Billiar TR. Early events in the recognition of danger signals after tissue injury. J Leukoc Biol 2008; 83:546-552. This review is a concise summary of the role of TLR-4 and molecular 'danger signals' (DAMPs) in models of injury, including hemorrhagic shock, femur fracture, and ischemia/reperfusion. It is a summary of recent data presented at the Seventh World Conference on Trauma, Shock, Inflammation, and Sepsis.
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This article describes the relationships between inflammation and angiogenesis in different locations within the joint affected by osteoarthritis
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Walsh DA, Bonnet CS, Turner EL, et al. Angiogenesis in the synovium and at the osteochondral junction in osteoarthritis. Osteoarthritis Cartilage 2007; 15:743-751. This article describes the relationships between inflammation and angiogenesis in different locations within the joint affected by osteoarthritis.
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Abdollahi-Roodsaz S, Joosten LA, Koenders MI, et al. Stimulation of TLR2 and TLR4 differentially skews the balance of T cells in a mouse model of arthritis. J Clin Invest 2008; 118:205-216. This interesting study demonstrates the complexity of TLR-2 and TLR-4 immunoregulation in a model of autoimmune arthritis. Evidence is presented that these TLRs may differentially drive regulatory versus inflammatory T-cell responses, suggesting there may be complex interaction between these two pathways in vivo. Although this is not an osteoarthritis model, the evidence presented has implications for TLR-mediated processes in other contexts that will need future clarification.
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52
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Bondeson J, Lauder S, Wainwright S, et al. Adenoviral gene transfer of the endogenous inhibitor IkappaBalpha into human osteoarthritis synovial fibro-blasts demonstrates that several matrix metalloproteinases and aggrecanases are nuclear factor-kappaB-dependent. J Rheumatol 2007; 34:523-533. This is a follow-up study to [52] that extends the authors' findings to aggrecanase activity, as well as cytokine-driven mediator production.
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Chen LX, Lin L, Wang HJ, Wei XL, et al. Suppression of early experimental osteoarthritis by in vivo delivery of the adenoviral vector-mediated NF-kappaBp65-specific siRNA. Osteoarthritis Cartilage 2008; 16:174-184. This is the first demonstration of NF-kB inhibition as a therapeutic strategy in a surgically induced rat model of osteoarthritis. It is a treatment study, as opposed to prevention, as NF-kB was inhibited after induction of disease. This treatment approach limited cartilage damage and synovial changes as observed 2 weeks after disease induction.
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Zhang Q, Hui W, Litherland GJ, et al. Differential Toll-like receptor-dependent collagenase expression in chondrocytes. Ann Rheum Dis 2008 [Epub ahead of print] doi:10.1136/ard.2007.079574. This very recent report is the first to show differential TLR expression in advanced osteoarthritis compared with normal cartilage, suggesting regulation of TLR activity in disease. In addition, the authors also demonstrate the ability of TLR-2 ligands to induce MMP-13 expression in chondrocytes.
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Zhang Q, Hui W, Litherland GJ, et al. Differential Toll-like receptor-dependent collagenase expression in chondrocytes. Ann Rheum Dis 2008 [Epub ahead of print] doi:10.1136/ard.2007.079574. This very recent report is the first to show differential TLR expression in advanced osteoarthritis compared with normal cartilage, suggesting regulation of TLR activity in disease. In addition, the authors also demonstrate the ability of TLR-2 ligands to induce MMP-13 expression in chondrocytes.
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61
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Magnano MD, Chakravarty EF, Broudy C, et al. A pilot study of tumor necrosis factor inhibition in erosive/inflammatory osteoarthritis of the hands. J Rheumatol 2007; 34:1323-1327. This is the pilot study using TNF-a inhibition in the treatment of erosive osteo-arthritis of the hands. Although this small study did not demonstrate efficacy using ACR20 response criteria, there was evidence of a substantial improvement in certain individuals. The choice of outcome measure and long-standing disease of the patients may have influenced the results, but positive trends in this small study support a role for TNF activity in certain patients.
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68
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Toll-like receptor 2 and 4 combination engagement upregulate IL-15 synergistically in human rheumatoid synovial fibroblasts
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Jung YO, Cho ML, Kang CM, et al. Toll-like receptor 2 and 4 combination engagement upregulate IL-15 synergistically in human rheumatoid synovial fibroblasts. Immunol Lett 2007; 109:21-27. This in-vitro study demonstrates the importance of TLR signaling in IL-15 production by synoviocytes.
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Roman-Blas JA, Stokes DG, Jimenez SA. Modulation of TGF-beta signaling by proinflammatory cytokines in articular chondrocytes. Osteoarthritis Cartilage 2007; 15:1367-1377. These authors demonstrate IL-1b and TNF-a can influence TGF-b signaling pathways in chondrocytes in vitro. This study points to the complexity of interactions between catabolic and anabolic influences that likely exists in vivo.
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Roman-Blas JA, Stokes DG, Jimenez SA. Modulation of TGF-beta signaling by proinflammatory cytokines in articular chondrocytes. Osteoarthritis Cartilage 2007; 15:1367-1377. These authors demonstrate IL-1b and TNF-a can influence TGF-b signaling pathways in chondrocytes in vitro. This study points to the complexity of interactions between catabolic and anabolic influences that likely exists in vivo.
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