4.7 Article

Synovial Fluid Cytokines, Chemokines and MMP Levels in Osteoarthritis Patients with Knee Pain Display a Profile Similar to Many Rheumatoid Arthritis Patients

Journal

JOURNAL OF CLINICAL MEDICINE
Volume 10, Issue 21, Pages -

Publisher

MDPI
DOI: 10.3390/jcm10215027

Keywords

synovial fluid; biomarkers; cytokines; osteoarthritis

Funding

  1. Advanced and Colorado Biologic Discovery Evaluation [HS 2511, HS 2847]
  2. Center for the Advancement of Science in Space (CASIS) NASA [NNH11CS70A, GA-2017-258 (HS 3095)]
  3. Investigator-Initiated OA SF biomarker grant by Fidia [HS 3179, NCT 04093232]

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This study compared the differences in synovial fluid cytokines and proteins between patients with osteoarthritis and rheumatoid arthritis. Results showed that osteoarthritis patients have a pro-inflammatory/catabolic synovial fluid environment, and the analysis of synovial fluid biomarkers may help distinguish different osteoarthritis phenotypes.
Background: There are currently no effective disease-modifying drugs to prevent cartilage loss in osteoarthritis and synovial fluid is a potentially valuable source of biomarkers to understand the pathogenesis of different types of arthritis and identify drug responsiveness. The aim of this study was to compare the differences between SF cytokines and other proteins in patients with OA (n = 21) to those with RA (n = 27) and normal knees (n = 3). Methods: SF was obtained using ultrasound (US) guidance and an external pneumatic compression device. RA patients were categorized as active (n = 20) or controlled (n = 7) based upon SF white blood cell counts (> or < 300 cells/mm(3)). Samples were cryopreserved and analyzed by multiplex fluorescent bead assays (Luminex). Between-group differences of 16 separate biomarker proteins were identified using ANOVA on log10-transformed concentrations with p values adjusted for multiple testing. Results: Only six biomarkers were significantly higher in SF from active RA compared to OA-TNF-alpha, IL-1-beta IL-7, MMP-1, MMP-2, and MMP-3. Only MMP-8 levels in RA patients correlated with SF WBC counts (p < 0.0001). Among OA patients, simultaneous SF IL-4, IL-6, IL-8, and IL-15 levels were higher than serum levels, whereas MMP-8, MMP-9, and IL-18 levels were higher in serum (p < 0.05). Conclusion: These results support the growing evidence that OA patients have a pro-inflammatory/catabolic SF environment. SF biomarker analysis using multiplex testing and US guidance may distinguish OA phenotypes and identify treatment options based upon targeted inflammatory pathways similar to patients with RA.

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