Arthritis research & therapy
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Arthritis Res. Ther. · Jan 2009
Reduced IgG anti-small nuclear ribonucleoprotein autoantibody production in systemic lupus erythematosus patients with positive IgM anti-cytomegalovirus antibodies.
Systemic lupus erythematosus is characterized by production of autoantibodies to RNA or DNA-protein complexes such as small nuclear ribonucleoproteins (snRNPs). A role of Epstein-Barr virus in the pathogenesis has been suggested. Similar to Epstein-Barr virus, cytomegalovirus (CMV) infects the majority of individuals at a young age and establishes latency with a potential for reactivation. Homology of CMV glycoprotein B (UL55) with the U1snRNP-70 kDa protein (U1-70 k) has been described; however, the role of CMV infection in production of anti-snRNPs is controversial. We investigated the association of CMV serology and autoantibodies in systemic lupus erythematosus. ⋯ Our findings suggest a potential role of CMV in regulation of autoantibodies to snRNPs and may provide a unique insight to understand the pathogenesis.
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Arthritis Res. Ther. · Jan 2009
Clinical TrialTreatment of focal degenerative cartilage defects with polymer-based autologous chondrocyte grafts: four-year clinical results.
Second-generation autologous chondrocyte implantation with scaffolds stabilizing the grafts is a clinically effective procedure for cartilage repair. In this ongoing prospective observational case report study, we evaluated the effectiveness of BioSeed-C, a cell-based cartilage graft based on autologous chondrocytes embedded in fibrin and a stable resorbable polymer scaffold, for the treatment of clinical symptomatic focal degenerative defects of the knee. ⋯ The results show that the good clinical outcome achieved 1 year after implantation of BioSeed-C remains stable over the course of a period of 4 years and suggest that implanting BioSeed-C is a promising treatment option for the repair of focal degenerative defects of the knee.
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Arthritis Res. Ther. · Jan 2009
Serum levels of soluble receptor for advanced glycation end products and of S100 proteins are associated with inflammatory, autoantibody, and classical risk markers of joint and vascular damage in rheumatoid arthritis.
The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily of cell surface receptor molecules. High concentrations of three of its putative proinflammatory ligands, S100A8/A9 complex (calprotectin), S100A8, and S100A12, are found in rheumatoid arthritis (RA) serum and synovial fluid. In contrast, soluble RAGE (sRAGE) may prevent proinflammatory effects by acting as a decoy. This study evaluated the serum levels of S100A9, S100A8, S100A12 and sRAGE in RA patients, to determine their relationship to inflammation and joint and vascular damage. ⋯ sRAGE and S100 proteins were associated not just with RA inflammation and autoantibody production, but also with classical vascular risk factors for end-organ damage. Consistent with its role as a RAGE decoy molecule, sRAGE had the opposite effects to S100 proteins in that S100 proteins were associated with autoantibodies and vascular risk, whereas sRAGE was associated with protection against joint and vascular damage. These data suggest that RAGE activity influences co-development of joint and vascular disease in rheumatoid arthritis patients.
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Arthritis Res. Ther. · Jan 2009
Intradiscal injection of simvastatin retards progression of intervertebral disc degeneration induced by stab injury.
Earlier work indicates that the cholesterol-lowering drug, simvastatin, is anabolic to chondrogenic expression of rat intervertebral disc (IVD) cells, which suggests a potential role for simvastatin in IVD regeneration. In this study, we expand on our earlier work to test the effectiveness of simvastatin on disc degeneration utilizing a rat tail disc degeneration model. ⋯ A single injection of simvastatin loaded in PEG-PLGA-PEG gel into rat tail discs had the potential to retard or regenerate the degenerative disc.
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Arthritis Res. Ther. · Jan 2009
Matrix metalloproteinase 28, a novel matrix metalloproteinase, is constitutively expressed in human intervertebral disc tissue and is present in matrix of more degenerated discs.
The regulation and elevation in expression of the catabolic matrix metalloproteinases (MMPs) is of high importance in the human intervertebral disc since upregulation of these matrix-degrading enzymes results in matrix destruction associated with disc degeneration. MMP28 (epilysin) is a newly discovered MMP believed to play a role in matrix composition and turnover in skin. It is present in basal keratinocytes where its expression is upregulated with wound repair, and in cartilage and synovium where it is upregulated in osteoarthritis. Recent work has shown that mechanical compression can act to modulate expression of MMP28. The expression of MMP28 is unexplored in the intervertebral disc. ⋯ Findings presented here show the first documentation of intervertebral disc expression and production of MMP28. MMP28 was found in both disc cell cytoplasm and in the ECM of more degenerated specimens, with greater cellular localization in the outer annulus and in herniated disc specimens. These findings are important because of the key role of MMPs in disc turnover and homeostasis, and previous indications of a role for this MMP in matrix repair and matrix turnover in other tissues. Our data, which show the presence of MMP28 in human disc tissue, suggest that MMP28 may have a potentially important role in ECM modulation in the healthy and degenerating disc.