Arthritis research & therapy
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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.
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Arthritis Res. Ther. · Jan 2009
Comparative StudyAssociation of common polymorphisms in known susceptibility genes with rheumatoid arthritis in a Slovak population using osteoarthritis patients as controls.
Both genetic and environmental factors contribute to rheumatoid arthritis (RA), a common and complex autoimmune disease. As well as the major susceptibility gene HLA-DRB1, recent genome-wide and candidate-gene studies reported additional evidence for association of single nucleotide polymorphism (SNP) markers in the PTPN22, STAT4, OLIG3/TNFAIP3 and TRAF1/C5 loci with RA. This study was initiated to investigate the association between defined genetic markers and RA in a Slovak population. In contrast to recent studies, we included intensively-characterized osteoarthritis (OA) patients as controls. ⋯ In our Slovak population, HLA-DRB1 alleles as well as SNPs in STAT4 and PTPN22 genes showed a strong association with RA.
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Arthritis Res. Ther. · Jan 2009
A functional difficulty and functional pain instrument for hip and knee osteoarthritis.
The objectives of this study were to develop a functional outcome instrument for hip and knee osteoarthritis research (OA-FUNCTION-CAT) using item response theory (IRT) and computer adaptive test (CAT) methods and to assess its psychometric performance compared to the current standard in the field. ⋯ The OA-FUNCTION-CAT provided superior reliability throughout the score range and improved breadth and precision at the ceiling compared with the WOMAC. Further research is needed to assess whether these improvements carry over into superior ability to measure change.
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Arthritis Res. Ther. · Jan 2009
Effect of interleukin-1beta on spinal cord nociceptive transmission of normal and monoarthritic rats after disruption of glial function.
Cytokines produced by spinal cord glia after peripheral injuries have a relevant role in the maintenance of pain states. Thus, while IL-1beta is overexpressed in the spinal cords of animals submitted to experimental arthritis and other chronic pain models, intrathecal administration of IL-1beta to healthy animals induces hyperalgesia and allodynia and enhances wind-up activity in dorsal horn neurons. ⋯ The results suggest that the excitatory effect of nanomolar doses of IL-1beta on spinal wind-up in healthy rats is produced by an unidentified glial mediator, while the inhibitory effects of IL-1beta on wind-up activity in animals with inactivated glia resulted from a direct effect of the cytokine on dorsal horn neurons. The present study failed to demonstrate a differential sensitivity of normal and monoarthritic rats to IL-1beta administration into the spinal cord and to disruption of beta glial function, as both normal and monoarthritic animals changes wind-up activity in the same direction after propentofylline treatment, suggesting that after glial inhibition normal and monoarthritic animals behave similarly relative to the capability of dorsal horn neurons to generate wind-up activity when repeatedly stimulated by C-fibers.
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Arthritis Res. Ther. · Jan 2008
Randomized Controlled Trial Multicenter StudyBiologic activity and safety of belimumab, a neutralizing anti-B-lymphocyte stimulator (BLyS) monoclonal antibody: a phase I trial in patients with systemic lupus erythematosus.
This trial evaluated the safety, biologic activity, and pharmacokinetics of belimumab, a fully human monoclonal antibody that inhibits the biologic activity of the soluble form of the essential B-cell survival factor B-lymphocyte stimulator (BLyS) in patients with systemic lupus erythematosus (SLE). ⋯ Belimumab was well tolerated and reduced peripheral B-cell levels in SLE patients. These data support further studies of belimumab in autoimmune disorders.