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

Richard T Meehan,Eric D Hoffman,John C Hill,Prashant J Parmar,Richard A Scheuring,Vijaya Knight,James L Crooks,Mary T Gill,Molly L Wolf,Elizabeth A Regan,Karin A Pacheco

doi:10.3390/jcm10215027

Abstract

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/mm3). 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-α, IL-1-β 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.

Highlights

IntroductionKnee OA is a growing problem worldwide due to aging populations, an increasing prevalence of obesity in developed countries, and even youth-related sports injuries [1,2,3]
In a study of 34 OA patients prior to knee arthroplasty for unicompartmental or bicompartment knee pain, Nees et al reported a significant correlation between radiographic OA severity and levels of IL-4, IL-6, IL-8, IFN gamma, SCGF-β, VEGF, and CXCLL01, whereas knee pain correlated with levels of IFN gamma, SCGFβ, and VEGF and with IL-7, IL-10, IL-12, and IL-13 levels [22]
We did observe a progressive increase in synovial fluid (SF) IL-6 levels between normal subjects, OA patients and controlled rheumatoid arthritis (RA) patients compared to active RA patients

Summary

Introduction

Knee OA is a growing problem worldwide due to aging populations, an increasing prevalence of obesity in developed countries, and even youth-related sports injuries [1,2,3]. It is associated with increasing health care costs and disability—in the US, 32 million have symptomatic activity limiting OA, with estimated direct medical costs exceeding $100 billion [4,5]. A critical need is the accurate identification of inflammatory arthritis of the knee, permitting disease-modifying treatments that could prevent disease progression and the need for joint replacement

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