Pain and functional limitations in knee osteoarthritis are reflected in the fatty acid composition of plasma extracellular vesicles.

This study investigated relationships between fatty acid (FA) profiles of extracellular vesicles (EVs) and cartilage degradation, functional limitations, pain, and psychological well-being in knee osteoarthritis (KOA). Fasting plasma was collected from controls (n = 10), end-stage KOA patients at baseline (n = 12) and at 3 and 12 months (n = 11 and 9) after joint replacement surgery, and from KOA synovial fluid (SF) at baseline (n = 10). EVs were isolated with the exoEasy Maxi Kit or size-exclusion chromatography, and EV FAs were analyzed with gas chromatography-mass spectrometry. Articular cartilage loss was determined by magnetic resonance imaging, and knee pain and function were assessed through questionnaires and physiatric and neuromuscular examinations. The associations of these data with EV FA proportions were tested with the univariate analysis of variance adjusted for age and body adiposity. Higher proportions of 16:1n-7, 18:1n-7, and total monounsaturated FAs in plasma EVs were associated with less severe KOA symptoms, while higher 24:1n-9, total saturated FAs, and ratios of arachidonic acid to long-chain n-3 polyunsaturated FAs (PUFAs) were linked to KOA pain, independent of age and body adiposity. In SF EVs, higher product/precursor ratios of n-6 PUFAs were associated with increased joint stiffness, and higher total dimethyl acetals were linked to physical disability. EV FAs emerged as significant indicators of knee pain and function. The results can be utilized to discover novel biomarkers for KOA and may have implications for targeted prevention and treatment of KOA symptoms by using EVs with a specific FA cargo.