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 16 weeks 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.

中文翻译：

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骨关节炎小鼠模型中与疼痛行为和病理相关的血浆脂质的脂质学鉴定。

简介骨关节炎（OA）是最常见的关节疾病，可引起疼痛和残疾。先前的研究表明脂质介质在OA发病机理中的作用。目的探讨已建立的OA模型小鼠血浆脂质组学特征的潜在改变，以鉴定疼痛和/或病理的潜在生物标志物。方法OA内侧半月板（DMM）模型失稳后评估疼痛行为（n = 8小鼠），并与假对照组（n = 7）进行比较。术后16周收集血浆和膝关节。使用多变量和单变量统计分析，使用超高效液相色谱精确质谱高分辨率质谱（UHPLC-HR-MS）分析血浆样品，以鉴定脂质组中的潜在差异。研究了疼痛行为，关节病理学和脂质水平之间的相关性。结果24种脂质主要来自胆固醇酯（CE），脂肪酸（FA），磷脂酰胆碱（PC），N-酰基乙醇胺（NAE）和鞘磷脂（SM），与假血浆相比差异表达。在DMM模型中增加的脂质中有6种被鉴定为CE（18：2），CE（20：4），CE（22：6），PC（18：0/18：2），PC（38： 7）和SM（d34：1）。CEs与疼痛行为呈正相关，所有六个脂质种类与软骨损伤均呈正相关。研究表明，与OA脂质稳态改变有关的途径是类固醇的生物合成和鞘脂代谢。结论我们在OA的DMM模型中鉴定了与疼痛和/或病理相关的血浆脂质种类。