Metabolomic analysis of human synovial fluid and plasma reveals that phosphatidylcholine metabolism is associated with both osteoarthritis and diabetes mellitus

This study was to investigate how OA patients with metabolic syndrome (MetS) are different metabolically from OA patients without MetS components and healthy individuals. A two-stage case–control study design was utilized. Synovial fluid (SF) and plasma samples were collected from patients undergoing total knee joint replacement due to primary OA and healthy controls (only plasma) and metabolically profiled using UPLC-MS coupled with assay kit which measures 186 metabolites. Orthogonal projection to latent structure-discriminant analysis and linear regression were used to identify metabolic markers for discriminating OA patients with MetS components from those without and healthy individuals. 54 paired SF and plasma samples from knee OA patients and 30 plasma samples from healthy controls were included in the discovery stage, and 143 plasma samples (72 from knee OA patients and 71 from the age, sex, and BMI matched controls) were included in the validation stage. OA patients with MetS can be clearly discriminated from OA patients without MetS based on the metabolite profiles of both SF and plasma and the separation appeared to be driven by type 2 diabetes but not obesity, hypertension, or dyslipidemia. When compared with OA patients with diabetes, OA without diabetes, and healthy controls, phosphatidylcholine acyl-alkyl C34:3 (PC ae C34:3) and phosphatidylcholine acyl-alkyl C36:3 (PC ae C36:3) were identified and confirmed to be associated with the concurrence of OA and diabetes (all p < 0.003). The study demonstrated that altered phosphatidylcholine metabolism was associated with both OA and diabetes mellitus.