Lipidomic identification of plasma lipids associated with pain behaviour and pathology in a mouse model of osteoarthritis

Pousinis, Petros; Gowler, Peter R. W.; Burston, James J.; Ortori, Catherine A.; Chapman, V.; Barrett, D. A.

Abstract

© 2020, The Author(s). Introduction: Osteoarthritis (OA) is the most common form of joint disease, causing pain and disability. Previous studies have demonstrated the role of lipid mediators in OA pathogenesis. Objectives: To explore potential alterations in the plasma lipidomic profile in an established mouse model of OA, with a view to identification of potential biomarkers of pain and/or pathology. Methods: Pain behaviour was assessed following destabilisation of the medial meniscus (DMM) model of OA (n = 8 mice) and compared to sham controls (n = 7). Plasma and knee joints were collected at 16weeks post-surgery. Plasma samples were analysed using ultra-high performance liquid chromatography accurate mass high resolution mass spectrometry (UHPLC-HR-MS) to identify potential differences in the lipidome, using multivariate and univariate statistical analyses. Correlations between pain behaviour, joint pathology and levels of lipids were investigated. Results: 24 lipids, predominantly from the lipid classes of cholesterol esters (CE), fatty acids (FA), phosphatidylcholines (PC), N-acylethanolamines (NAE) and sphingomyelins (SM), were differentially expressed in DMM plasma compared to sham plasma. Six of these lipids which were increased in the DMM model were identified as CE(18:2), CE(20:4), CE(22:6), PC(18:0/18:2), PC(38:7) and SM(d34:1). CEs were positively correlated with pain behaviour and all six lipid species were positively correlated with cartilage damage. Pathways shown to be involved in altered lipid homeostasis in OA were steroid biosynthesis and sphingolipid metabolism. Conclusion: We identify plasma lipid species associated with pain and/or pathology in a DMM model of OA.

Citation

Pousinis, P., Gowler, P. R. W., Burston, J. J., Ortori, C. A., Chapman, V., & Barrett, D. A. (2020). Lipidomic identification of plasma lipids associated with pain behaviour and pathology in a mouse model of osteoarthritis. Metabolomics, 16(3), Article 32 (2020). https://doi.org/10.1007/s11306-020-01652-8

• Journal Article Type: Article
• Acceptance Date: Feb 19, 2020
• Online Publication Date: Feb 27, 2020
• Publication Date: Mar 1, 2020
• Deposit Date: Feb 27, 2020
• Publicly Available Date: Feb 27, 2020
• Journal: Metabolomics
• Electronic ISSN: 1573-3890
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 16
• Issue: 3
• Article Number: 32 (2020)
• DOI: https://doi.org/10.1007/s11306-020-01652-8
• Keywords: Osteoarthritis; Pain; LC-MS Lipidomics; Destabilisation of the Medial Meniscus
• Public URL: https://nottingham-repository.worktribe.com/output/4045581
• Publisher URL: https://link.springer.com/article/10.1007%2Fs11306-020-01652-8