Arthritis research & therapy
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Arthritis Res. Ther. · Jan 2011
Effects of Wnt3A and mechanical load on cartilage chondrocyte homeostasis.
Articular cartilage functions in withstanding mechanical loads and provides a lubricating surface for frictionless movement of joints. Osteoarthritis, characterised by cartilage degeneration, develops due to the progressive erosion of structural integrity and eventual loss of functional performance. Osteoarthritis is a multi-factorial disorder; two important risk factors are abnormal mechanical load and genetic predisposition. A single nucleotide polymorphism analysis demonstrated an association of hip osteoarthritis with an Arg324Gly substitution mutation in FrzB, a Wnt antagonist. The purpose of this study was two-fold: to assess whether mechanical stimulation modulates β-catenin signalling and catabolic gene expression in articular chondrocytes, and further to investigate whether there is an interplay of mechanical load and Wnt signalling in mediating a catabolic response. ⋯ Our data suggest that load and Wnt, in combination, can repress transcription of chondrocyte matrix genes, whilst enhancing expression of catabolic mediators. Future studies will investigate the respective roles of abnormal loading and genetic predisposition in mediating cartilage degeneration.
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Arthritis Res. Ther. · Jan 2011
Videoradiographic analysis of the range of motion in unilateral experimental knee joint arthritis in rats.
The translational and predictive value of animal models highly depends on the validity of respective readout parameters. In arthritis research, there has been a shift from sole threshold testing for pain-related behavior, as well as from swelling and histology assessment for inflammation, toward an analysis of joint function as indicated, for instance, by an increasing number of studies on gait abnormalities. Clinically, the range of motion (ROM) of the affected joint plays a major role in diagnosis and the assessment of treatment benefits. This parameter, however, is only insufficiently detected by currently used analytic systems in animals. ⋯ The dynamic ROM observed in freely moving rats in our model of knee joint arthritis might serve as a parameter for global disease activity and might thus represent a promising readout parameter for preclinical assessment regarding the overall efficacy not only of antiarthritic but also of antinociceptive compounds.
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Arthritis Res. Ther. · Jan 2011
Predictors for pathologically confirmed aortitis after resection of the ascending aorta: a 12-year Danish nationwide population-based cross-sectional study.
Assessing the prevalence of, and predictors for, pathologically-confirmed inflammation of the aorta in Denmark, using a nationwide population-based study design. ⋯ Aortitis was present in 6.1% of adults in Denmark who had pathological examination after resection of the ascending aorta. Predictors of inflammation included connective tissue disease, diabetes, advanced age, and aortic valve pathology.
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Arthritis Res. Ther. · Jan 2011
Editorial CommentBeyond cognitive-behavioral therapy for fibromyalgia: addressing stress by emotional exposure, processing, and resolution.
I comment on the well-designed trial by Alda and colleagues reported in a recent issue of Arthritis Research and Therapy which demonstrated some benefits of cognitive-behavioral therapy (CBT) for fibromyalgia (FM). CBT in this and other studies provides statistically significant but rather modest benefits for FM. This may be because CBT does not directly address the high rates of victimization, post-traumatic stress disorder, and emotional avoidance experienced by a substantial number of patients with FM. Interventions that encourage emotional exposure, processing, and resolution of stressful or traumatic experiences and relationships hold potential for larger effects for many patients and need to be tested.
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Arthritis Res. Ther. · Jan 2011
The efficacy of Link N as a mediator of repair in a rabbit model of intervertebral disc degeneration.
Intervertebral disc (IVD) degeneration is associated with proteolytic degradation of the extracellular matrix, and its repair requires both the production of extracellular matrix and the downregulation of proteinase activity. These properties are associated with several growth factors. However, the use of growth factors in clinical practice is limited by their high cost. This cost can be circumvented using synthetic peptides, such as Link N, which can stimulate the synthesis of proteoglycan and collagen by IVD cells in vitro. The purpose of the present study was to evaluate the effect of Link N in vivo in a rabbit model of IVD degeneration. ⋯ When administered to the degenerate disc in vivo, Link N stimulated aggrecan gene expression and downregulated metalloproteinase expression, and there was a trend towards increased proteoglycan content of the disc, in both the NP and AF. These are features needed for any agent designed to stimulate disc repair. In principle, therefore, Link N supplementation could be an option for treating disc degeneration.