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.

Keywords

Osteoarthritis; Inflammation; Extracellular matrix; Chondrocyte

Published in

Research in Veterinary Science
2018, Volume: 118, pages: 466-476
Publisher: ELSEVIER SCI LTD

SLU Authors

• Löfgren, Maria

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    

• Svala, Emilia

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    
  • University of Gothenburg

• Skiöldebrand, Eva

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    
  • University of Gothenburg

• Ekman, Stina

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    

UKÄ Subject classification

Medical Bioscience


Publication identifier

DOI: https://doi.org/10.1016/j.rvsc.2018.04.013

Permanent link to this page (URI)

https://res.slu.se/id/publ/95855