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Time-dependent changes in gene expression induced in vitro by interleukin-1 beta in equine articular cartilage

Journal article
Authors M. Lofgren
Emilia Svala
Anders Lindahl
Eva Skiöldebrand
S. Ekman
Published in Research in Veterinary Science
Volume 118
Pages 466-476
ISSN 0034-5288
Publication year 2018
Published at Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine
Pages 466-476
Language en
Links https://doi.org/10.1016/j.rvsc.2018...
Keywords Osteoarthritis, Inflammation, Extracellular matrix, Chondrocyte, chondrocyte differentiation pathway, ii collagen gene, rheumatoid-arthritis, pericellular matrix, candidate genes, osteoarthritis, perlecan, sox9, proteoglycan, notch, Veterinary Sciences
Subject categories Veterinary Science

Abstract

Osteoarthritis is an inflammatory and degenerative joint disease commonly affecting horses. To identify genes of relevance for cartilage pathology in osteoarthritis we studied the time-course effects of interleukin (IL)-1 beta on equine articular cartilage. Articular cartilage explants from the distal third metacarpal bone were collected postmortem from three horses without evidence of joint disease. The explants were stimulated with IL-1 beta for 27 days and global gene expression was measured by microarray. Gene expression was compared to that of unstimulated explants at days 3, 9, 15, 21 and 27. Release of inflammatory proteins was measured using Proximity Extension Assay. Stimulation with IL-1 beta led to time-dependent changes in gene expression related to inflammation, the extracellular matrix (ECM), and phenotypic alterations. Gene expression and protein release of cytokines, chemokines, and matrix-degrading enzymes increased in the stimulated explants. Collagen type II was down regulated from day 15, whereas other ECM molecules were downregulated earlier. In contrast molecules involved in ECM signaling (perlecan, chondroitin sulfate proteoglycan 4, and syndecan 4) were upregulated. At the late time points, genes related to a chondrogenic phenotype were downregulated, and genes related to a hypertrophic phenotype were upregulated, suggesting a transition towards hypertrophy later in the culturing period. The data suggest that this in vitro model mimics time course events of in vivo inflammation in OA and it may be valuable as an in vitro tool to test treatments and to study disease mechanisms.

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