Journal article
Time-dependent changes in gene expression induced in vitro by interleukin-1β in equine articular cartilage
Research in veterinary science, Vol.118, pp.466-476
06/01/2018
DOI: 10.1016/j.rvsc.2018.04.013
PMID: 29747133
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)-1β 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-1β 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-1β 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 downregulated 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.
•Stimulation of equine articular cartilage explants with interleukin-1β during 27 days leads to changes in gene expression•Inflammatory mediators and matrix-degrading enzymes were upregulated in interleukin-1β stimulated cartilage explants•Gene expression of extracellular matrix molecules related to the collagen network was downregulated in stimulated explants•Evidence of a chondrogenic phenotype early with transition towards hypertrophy later during culture was observed•The in vitro results mimic the time course events of inflammation found in osteoarthritic joints in vivo
Details
- Title: Subtitle
- Time-dependent changes in gene expression induced in vitro by interleukin-1β in equine articular cartilage
- Creators
- Maria Löfgren - Swedish University of Agricultural SciencesEmilia Svala - Swedish University of Agricultural SciencesAnders Lindahl - Sahlgrenska University HospitalEva Skiöldebrand - Swedish University of Agricultural SciencesStina Ekman - Swedish University of Agricultural Sciences
- Resource Type
- Journal article
- Publication Details
- Research in veterinary science, Vol.118, pp.466-476
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/j.rvsc.2018.04.013
- PMID
- 29747133
- ISSN
- 0034-5288
- eISSN
- 1532-2661
- Grant note
- name: Swedish Norwegian Foundation, award: H0847237; DOI: 10.13039/501100001862, name: The Swedish Research Council Formas, award: 221-2013-317
- Language
- English
- Date published
- 06/01/2018
- Academic Unit
- Nursing
- Record Identifier
- 9984370462802771
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