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

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Abstract

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.

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Acknowledgments

We thank all the study participants who made this study possible, and all the staff who helped us in the collection of samples. The study was funded by Canadian Institutes of Health Research (CIHR), Newfoundland & Labrador RDC, and Memorial University.

Financial support

Canadian Institutes of Health Research (CIHR); Newfoundland & Labrador RDC; Memorial University of Newfoundland

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Authors and Affiliations

  1. Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St John’s, NL, A1B 3V6, Canada

    Weidong Zhang, Erfan Aref-Eshghi, Patricia E. Harper, Roger Green & Guangju Zhai

  2. Discipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland, St John’s, NL, Canada

    Guang Sun & Proton Rahman

  3. Department of Laboratory Medicine, Faculty of Medicine, Memorial University of Newfoundland, St John’s, NL, Canada

    Sergei Likhodii & Edward Randell

  4. Department of Surgery, Faculty of Medicine, Memorial University of Newfoundland, St John’s, NL, Canada

    Glynn Martin & Andrew Furey

  5. Department of Twin Research & Genetic Epidemiology, King’s College London, London, UK

    Guangju Zhai

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  1. Weidong Zhang
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  2. Guang Sun
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  3. Sergei Likhodii
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  4. Erfan Aref-Eshghi
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  7. Roger Green
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Correspondence to Guangju Zhai.

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The study was approved by the Health Research Ethics Authority (HREA) of Newfoundland and Labrador and written consent was obtained from all the participants.

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Roger Green—Deceased.

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Zhang, W., Sun, G., Likhodii, S. et al. Metabolomic analysis of human synovial fluid and plasma reveals that phosphatidylcholine metabolism is associated with both osteoarthritis and diabetes mellitus. Metabolomics 12, 24 (2016). https://doi.org/10.1007/s11306-015-0937-x

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