| 1. |
- Nielsen, Morten A., et al.
(författare)
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Increased Galectin-9 Levels Correlate with Disease Activity in Patients with DMARD-Naïve Rheumatoid Arthritis and Modulate the Secretion of MCP-1 and IL-6 from Synovial Fibroblasts
- 2023
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fibroblast-like synoviocytes (FLSs) are essential mediators in the expansive growth and invasiveness of rheumatoid synovitis, and patients with a fibroblastic-rich pauci-immune pathotype respond poorly to currently approved antirheumatic drugs. Galectin-9 (Gal-9) has been reported to directly modulate rheumatoid arthritis (RA) FLSs and to hold both pro- and anti-inflammatory properties. The objective of this study was to evaluate clinical and pathogenic aspects of Gal-9 in RA, combining national patient cohorts and cellular models. Methods: Soluble Gal-9 was measured in plasma from patients with newly diagnosed, treatment-naïve RA (n = 98). The disease activity score 28-joint count C-reactive protein (DAS28CRP) and total Sharp score were used to evaluate the disease course serially over a two-year period. Plasma and synovial fluid samples were examined for soluble Gal-9 in patients with established RA (n = 18). A protein array was established to identify Gal-9 binding partners in the extracellular matrix (ECM). Synovial fluid mononuclear cells (SFMCs), harvested from RA patients, were used to obtain synovial-fluid derived FLSs (SF-FLSs) (n = 7). FLSs from patients suffering from knee Osteoarthritis (OA) were collected from patients when undergoing joint replacement surgery (n = 5). Monocultures of SF-FLSs (n = 6) and autologous co-cultures of SF-FLSs and peripheral blood mononuclear cells (PBMCs) were cultured with and without a neutralizing anti-Gal-9 antibody (n = 7). The mono- and co-cultures were subsequently analyzed by flow cytometry, MTT assay, and ELISA. Results: Patients with early and established RA had persistently increased plasma levels of Gal-9 compared with healthy controls (HC). The plasma levels of Gal-9 were associated with disease activity and remained unaffected when adding a TNF-inhibitor to their standard treatment. Gal-9 levels were elevated in the synovial fluid of established RA patients with advanced disease, compared with corresponding plasma samples. Gal-9 adhered to fibronectin, laminin and thrombospondin, while not to interstitial collagens in the ECM protein array. In vitro, a neutralizing Gal-9 antibody decreased MCP-1 and IL-6 production from both RA FLSs and OA FLSs. In co-cultures of autologous RA FLSs and PBMCs, the neutralization of Gal-9 also decreased MCP-1 and IL-6 production, without affecting the proportion of inflammatory FLSs. Conclusions: In RA, pretreatment plasma Gal-9 levels in early RA were increased and correlated with clinical disease activity. Gal-9 levels remained increased despite a significant reduction in the disease activity score in patients with early RA. The in vitro neutralization of Gal-9 decreased both MCP-1 and IL-6 production in an inflammatory subset of RA FLSs. Collectively these findings indicate that the persistent overexpression of Gal-9 in RA may modulate synovial FLS activities and could be involved in the maintenance of subclinical disease activity in RA.
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| 2. |
- Svendsen, Susanne Wulff, et al.
(författare)
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Work above shoulder level and degenerative alterations of the rotator cuff tendons : a magnetic resonance imaging study.
- 2004
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Ingår i: Arthritis and rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 50:10, s. 3314-22
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine whether work performed with the arms in a highly elevated position is associated with alterations in the rotator cuff tendons as assessed by magnetic resonance imaging (MRI). METHODS: A cross-sectional study was performed in a historical cohort of male machinists, car mechanics, and house painters. The participants were right-handed, ages 40-50 years, and had been employed in their trades for not less than 10 years. Seventy-one percent of invited subjects participated (136 of 192). Lifetime upper arm elevation was assessed by direct measurements combined with individual work histories obtained by questionnaire and from registry data. Supraspinatus tendinopathy was evidenced by MRI signal intensity changes and morphologic alterations. Infraspinatus and subscapularis tendinopathy were also assessed. Additional outcomes were acromioclavicular joint degeneration and humeral head cysts. The MRI findings were evaluated by radiologists who were blinded to exposure status and symptoms. RESULTS: An exposure-response relationship was found between lifetime upper arm elevation and supraspinatus tendinopathy, with an age-adjusted odds ratio of 1.27 (95% confidence interval 1.02-1.60) for a 5-month increase in the total number of full-time working months spent with the arm elevated >90 degrees . CONCLUSION: Work with the arms in a highly elevated position is associated with MRI-diagnosed alterations in the supraspinatus tendon. By demonstrating the first part of a possible biologic pathway, the study corroborates the work-relatedness of rotator cuff disorders.
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