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Regulation of fibronectin and collagens type I, III and VI by TNF-α, TGF-β, IL-13, and tofacitinib.

January 7, 2025

Sci Rep

Abstract Understanding how inflammatory cytokines influence profibrogenic wound healing responses in fibroblasts is important for understanding the pathogenesis of fibrosis. TNF-α and IL-13 are key cytokines in Th1 and Th2 immune responses, respectively, while TGF-β1 is the principal pro-fibrotic mediator. We show that 12-day fibroblast culture with TNF-α or IL-13 induces fibrogenesis, marked by progressively […]

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A novel biomarker of MMP-cleaved cartilage intermediate layer protein-1 is elevated in patients with rheumatoid arthritis, ankylosing spondylitis and osteoarthritis.

December 7, 2023

Sci Rep

Abstract Rheumatic joints have an altered cartilage turnover. Cartilage intermediate layer protein 1 (CILP-1) is secreted from articular chondrocytes and deposited into the cartilage extracellular matrix. We developed an immunoassay targeting a Matrix Metalloproteinase (MMP)-generated neo-epitope of CILP-1, named CILP-M. Human articular cartilage was cleaved with proteolytic enzymes and CILP-M levels were measured. We also […]

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Extracellular matrix turnover biomarkers reflect pharmacodynamic effects and treatment response of adalimumab in patients with axial spondyloarthritis-results from two randomized controlled trials.

August 25, 2023

Arthritis Res Ther

Abstract OBJECTIVE To investigate if extracellular matrix (ECM) blood-based biomarkers reflect the pharmacodynamic effect and response to TNF-α inhibitor therapy (adalimumab, ADA), in patients with axial spondyloarthritis (axSpA). METHODS We investigated ECM biomarkers in two randomized, double-blind, placebo-controlled trials of axSpA patients (DANISH and ASIM, n = 52 and n = 49, respectively) receiving ADA 40 mg or placebo every […]

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The Citrullinated and MMP-degraded Vimentin Biomarker (VICM) Predicts Early Response to Anti-TNFα Treatment in Crohn’s Disease.

January 1, 2021

J Clin Gastroenterol

Abstract BACKGROUND In Crohn’s disease (CD), 10% to 40% of patients do not respond to anti-tumor necrosis factor-α (TNFα) treatment. Currently, there are no biomarkers with adequate sensitivity to separate responders from nonresponders at an early stage. AIM The aim of this study was to investigated whether early changes in the VICM (citrullinated and matrix […]

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Serological Biomarkers of Tissue Turnover Identify Responders to Anti-TNF Therapy in Crohn’s Disease: A Pilot Study.

September 1, 2020

Clin Transl Gastroenterol

Abstract INTRODUCTION Anti-tumor necrosis factor (TNF) therapy is effective in inducing remission in Crohn’s disease in 60% of patients. No serological biomarkers are available, which can predict response to anti-TNF. We aimed to investigate serological markers of collagen turnover reflecting tissue inflammation as predictors of response to anti-TNF. METHODS In 2 retrospective observational cohorts, markers […]

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Inflammation and joint destruction may be linked to the generation of cartilage metabolites of ADAMTS-5 through activation of toll-like receptors.

May 1, 2020

Osteoarthritis Cartilage

Abstract OBJECTIVE Links between pain and joint degradation are poorly understood. We investigated the role of activation of Toll-like receptors (TLR) by cartilage metabolites in initiating and maintaining the inflammatory loop in OA causing joint destruction. METHODS Synovial membrane explants (SMEs) were prepared from OA patients’ synovial biopsies. SMEs were cultured for 10 days under […]

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IL-6 receptor inhibition modulates type III collagen and C-reactive protein degradation in rheumatoid arthritis patients with an inadequate response to anti-tumour necrosis factor therapy: analysis of connective tissue turnover in the tocilizumab RADIATE study.

August 1, 2018

Clin Exp Rheumatol

Abstract OBJECTIVES The objective of this study was to examine the tissue degradation in response to anti-IL6 receptor treatment in rheumatoid arthritis (RA) patients which are anti-TNF-α inadequate responders. METHODS RADIATE was a randomised, double-blinded, placebo-controlled, parallel-group, phase III trial. RA patients with previous inadequate response to anti-TNFα therapy (n=299) were randomly assigned to tocilizumab […]

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The active form of MMP-3 is a marker of synovial inflammation and cartilage turnover in inflammatory joint diseases.

March 19, 2014

BMC Musculoskelet Disord

Abstract BACKGROUND Matrix metalloproteinase-3 (MMP-3) plays an important role in the pathology of rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Measurement of active MMP-3 in clinical samples could provide information about progression of rheumatoid diseases, and potentially response to treatment. Hence, we aimed to develop a sensitive assay specifically measuring the active form of MMP-3 […]

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Investigation of chondrocyte hypertrophy and cartilage calcification in a full-depth articular cartilage explants model.

February 1, 2013

Rheumatol Int

Abstract Articular cartilage deterioration, which includes cartilage degradation and chondrocyte hypertrophy, is a hallmark of degenerative joint diseases (DJD). Chondrocyte hypertrophy is initiated in the deep layer of the cartilage; thus, a robust explants model for investigation of hypertrophy should include this zone. The aim of this study was to characterize and investigate the hypertrophy-promoting […]

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