Arthritis and rheumatism
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Arthritis and rheumatism · Jan 2008
Sphingomyelinase decreases type II collagen expression in bovine articular cartilage chondrocytes via the ERK signaling pathway.
Ceramide, a mediator of proinflammatory cytokine signaling, induces cartilage degradation and reduces type II collagen synthesis in articular cartilage. The accumulation of ceramide is associated with arthritis in Farber's disease. The aim of this study was to investigate the mechanism of ceramide-induced down-regulation of type II collagen. ⋯ SMase down-regulates type II collagen in articular chondrocytes via activation of the ERK signaling cascade, redistribution of SOX9, and recruitment of c-Fos. This new mechanism for cartilage degradation provides potential targets for future treatment of arthritic disease.
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Arthritis and rheumatism · Jan 2008
High N-terminal pro-brain natriuretic peptide levels and low diffusing capacity for carbon monoxide as independent predictors of the occurrence of precapillary pulmonary arterial hypertension in patients with systemic sclerosis.
To evaluate predictors of pulmonary arterial hypertension (PAH) in a prospective cohort of patients with systemic sclerosis (SSc). ⋯ This prospective study identified a decreased DLCO/VA ratio and an increased NT-proBNP as predictors of PAH in SSc. Use of these markers should result in improved PAH risk stratification and allow earlier initiation of therapy.
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Arthritis and rheumatism · Jan 2008
Abnormal tumor necrosis factor receptor I cell surface expression and NF-kappaB activation in tumor necrosis factor receptor-associated periodic syndrome.
Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is an autosomal-dominant autoinflammatory condition caused by mutations in the TNFRSF1A gene. The cellular mechanisms by which mutations in this gene trigger inflammation are currently unclear. Because NF-kappaB is the major intracellular signaling component inducing secretion of proinflammatory cytokines, we sought to determine whether differences in the clinical phenotype of patients with TRAPS may be attributable to variable effects of TNFRSF1A mutations on TNFRI expression, localization, or NF-kappaB activity. ⋯ High levels of TNFRI at the cell surface in patients with the C73R mutation hypersensitizes cells to stimulation by TNF, leading to increased NF-kappaB p65 subunit activation and an exaggerated proinflammatory response.
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Arthritis and rheumatism · Jan 2008
Cannabinoid-mediated antinociception is enhanced in rat osteoarthritic knees.
To determine whether local administration of the cannabinoid 1 (CB(1)) receptor agonist arachidonyl-2-chloroethylamide (ACEA) can modulate joint nociception in control rat knee joints and in experimental osteoarthritis (OA). ⋯ These findings indicate that activation of peripheral CB(1) receptors reduces the mechanosensitivity of afferent nerve fibers in control and OA knee joints. Blockade of either the CB(1) receptor or the TRPV-1 channel significantly reduced the efficacy of ACEA, which suggests that both receptors are involved in cannabinoid-mediated antinociception. The increased nerve activity observed following CB(1) receptor antagonism suggests a tonic release of endocannabinoids during OA. As such, peripheral CB(1) receptors may be important targets in controlling OA pain.