Ex-Vivo Equine Cartilage Explant Osteoarthritis Model - A Metabolomics and Proteomics Study.



Anderson, James R ORCID: 0000-0003-0489-7997, Phelan, Marie M, Foddy, Laura, Clegg, Peter D and Peffers, Mandy J ORCID: 0000-0001-6979-0440
(2020) Ex-Vivo Equine Cartilage Explant Osteoarthritis Model - A Metabolomics and Proteomics Study. Journal of proteome research, 19 (9). pp. 3652-3667.

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Abstract

Osteoarthritis is an age-related degenerative musculoskeletal disease characterised 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 TNF-α/IL-1β supplemented culture media for 8 days, with 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 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 whilst adenosine, alanine, betaine, creatine, myo-inositol and uridine decreased. Within the culture media, four, four and six differentially abundant metabolites and 154, 138 and 72 differentially abundant proteins were identified at 1-2 days, 3-5 days 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 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.

Item Type: Article
Uncontrolled Keywords: osteoarthritis, cartilage, metabolomics, proteomics, nuclear magnetic resonance, mass spectrometry
Depositing User: Symplectic Admin
Date Deposited: 03 Aug 2020 09:27
Last Modified: 18 Jan 2023 23:38
DOI: 10.1021/acs.jproteome.0c00143
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3096213