Abstract
We investigated the associations of pro- and anti-inflammatory fatty acids (FAs) with cartilage degradation, functional limitations, pain, and psychological well-being in knee osteoarthritis (KOA). Fasting plasma samples were obtained from controls (n = 12) and from end-stage KOA patients at baseline (n = 13), and 3 months (n = 11) and 12 months (n = 9) after knee replacement surgery. FA composition in total lipids was analyzed with gas chromatography and mass spectrometry. Cartilage loss was determined by magnetic resonance imaging, and knee pain and disability by physical performance and quantitative sensory testing, neuromuscular examination, and several questionnaires. The associations between variables were tested with the univariate analysis of variance adjusted for age and body mass index. KOA was characterized with elevated baseline 16:1n-7 percentages, while the proportions of 24:0 decreased 12 months after surgery and those of 24:1n-9 decreased 3 and 12 months after surgery. Several FA variables, such as 20:3n-6, 20:4n-6, long-chain saturated FAs, and 24:1n-9, were associated with pain, stiffness, disability, pain self-efficacy, or mental health. Circulating FAs can predict KOA symptoms, independent of age and body adiposity, and provide promising targets to design novel pain treatments.
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Data availability
All relevant data analyzed during this study are included in this published article and its supplementary information files.
Abbreviations
- ANOVA:
-
Analysis of variance
- BAI:
-
Beck anxiety inventory
- BDI:
-
Beck depression inventory
- BMI:
-
Body mass index
- CE:
-
Cholesterol ester
- DA:
-
Discriminant analysis
- DI:
-
Desaturation index
- DMA:
-
Dimethyl acetal
- FA:
-
Fatty acid
- FAME:
-
Fatty acid methyl ester
- GLM:
-
Generalized linear model
- IL:
-
Interleukin
- KOA:
-
Knee osteoarthritis
- LICI:
-
Long-interval cortical inhibition
- LM:
-
Lipid mediator
- MRI:
-
Magnetic resonance imaging
- MUFA:
-
Monounsaturated fatty acid
- NSAID:
-
Non-steroidal anti-inflammatory drug
- nTMS:
-
Navigated transcranial magnetic stimulation
- OA:
-
Osteoarthritis
- PL:
-
Phospholipid
- PPT:
-
Pressure pain threshold
- PSEQ:
-
Pain self-efficacy questionnaire
- PUFA:
-
Polyunsaturated fatty acid
- RA:
-
Rheumatoid arthritis
- rMT:
-
Resting motor threshold
- ROM:
-
Range of motion
- rs :
-
Spearman correlation coefficient
- Rv:
-
Resolvin
- SE:
-
Standard error of the mean
- SF:
-
Synovial fluid
- SFA:
-
Saturated fatty acid
- TKA:
-
Total knee arthroplasty
- TNF-α :
-
Tumor necrosis factor-α
- TPD:
-
Two-point discrimination
- VAS:
-
Visual analog scale
- WOMAC:
-
Western Ontario and McMaster Universities Osteoarthritis Index
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Acknowledgements
Taija Hukkanen is greatly acknowledged for the blood sampling and transmethylation of the samples, and Meri Julkunen and Anna-Leena Voutilainen for coordinating the study. We are also thankful for Heikki Kyykallio, Johanna Matilainen, and Tommi Paakkonen for technical assistance.
Funding
Financial support for the study was provided by the Research Council of Finland (grant #322429). The funding source had no involvement in the study design, in the collection, analysis, and interpretation of data, in the writing of the report, or in the decision to submit the article for publication.
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PN, PJ, HK, and JA designed and coordinated the study. HK collected the samples, and LS, JR, and PJ conducted the physical analyses and LK the physiatric measurements. JR performed the magnetic resonance imaging, and AE determined the thickness of articular cartilage. RK and SPS performed the fatty acid analyses. PN integrated the chromatograms, and PN, A-MM, and JK conducted the statistical analyses and prepared the images. A-MM drafted the manuscript. All authors revised the draft critically and read and approved the final submitted manuscript.
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Petro Julkunen reports unrelated consulting fees and a patent with Nexstim Plc (Helsinki, Finland), a manufacturer of navigated transcranial magnetic stimulation systems. Jusa Reijonen reports unrelated consulting fees with Nexstim Plc. The other authors have no relevant financial or non-financial interests to disclose.
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This study was performed in line with the principles of the Declaration of Helsinki. Ethical approval was obtained from the Ethical Committee of Kuopio University Hospital (decision #140/2017, amendment 8/2020). Informed consent was obtained from all individual participants included in the study.
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Mustonen, AM., Säisänen, L., Karttunen, L. et al. Plasma fatty acids reflect pain, disability, and psychological well-being in knee osteoarthritis in a longitudinal study with joint replacement surgery. Sci Rep (2026). https://doi.org/10.1038/s41598-026-36812-8
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DOI: https://doi.org/10.1038/s41598-026-36812-8


