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Ex Vivo Equine Cartilage Explant Osteoarthritis Model: A Metabolomics and Proteomics Study
journal contribution
posted on 2020-08-06, 22:19 authored by James R. Anderson, Marie M. Phelan, Laura Foddy, Peter D. Clegg, Mandy J. PeffersOsteoarthritis is an age-related
degenerative musculoskeletal disease
characterized by loss of articular cartilage, synovitis, and subchondral
bone sclerosis. Osteoarthritis pathogenesis is yet to be fully elucidated
with no osteoarthritis-specific biomarkers in clinical use. Ex vivo equine cartilage explants (n =
5) were incubated in tumor necrosis factor-α (TNF-α)/interleukin-1β
(IL-1β)-supplemented culture media for 8 days, with the media
removed and replaced at 2, 5, and 8 days. Acetonitrile metabolite
extractions of 8 day cartilage explants and media samples at all time
points underwent one-dimensional (1D) 1H nuclear magnetic
resonance metabolomic analysis, with media samples also undergoing
mass spectrometry proteomic analysis. Within the cartilage, glucose
and lysine were elevated following TNF-α/IL-1β treatment,
while adenosine, alanine, betaine, creatine, myo-inositol, and uridine
decreased. Within the culture media, 4, 4, and 6 differentially abundant
metabolites and 154, 138, and 72 differentially abundant proteins
were identified at 1–2, 3–5, and 6–8 days, respectively,
including reduced alanine and increased isoleucine, enolase 1, vimentin,
and lamin A/C following treatment. Nine potential novel osteoarthritis
neopeptides were elevated in the treated media. Implicated pathways
were dominated by those involved in cellular movement. Our innovative
study has provided insightful information on early osteoarthritis
pathogenesis, enabling potential translation for clinical markers
and possible new therapeutic targets.
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tumor necrosis factor -α8 day cartilage explantsAcetonitrile metabolite extractionssubchondral bone sclerosisEx Vivo Equine Cartilage Explant Os...8 daysProteomics Study OsteoarthritisTNFILmass spectrometry proteomic analysisresonance metabolomic analysisnovel osteoarthritis neopeptidesmedia samplesEx vivo equine cartilage explants
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