Serum Inflammatory Markers in Patients with Knee Osteoarthritis: A Proteomic Approach

OBJECTIVES: Osteoarthritis (OA) is known to be a slowly progressive disease that alters all tissue compartments of the joint involved with a characteristic degradation of the cartilage, bone remodeling, and inflammation. One of the prominent symptoms in OA patients is pain, but a few radiological, inflammatory or structurally related biomarkers have shown little if any associations to pain. This study aimed to assess serum levels of 92 markers involved in inflammatory pathways in patients with knee OA (KOA) and evaluate their possible associations with the clinical pain intensity.

METHODS: Serum samples were collected from 127 knee KOA patients and 39 healthy participants with no knee pain. Each serum sample was analyzed for 92 inflammatory markers using the Proximity Extension Array (PEA) technology. Clinical pain intensity was assessed using a visual analog scale, and patients completed the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire.

RESULTS: Fifteen markers were significantly different when comparing KOA patient and healthy participants. Two markers, fibroblast growth factor-21 (FGF-21) and Eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), correlated positively with pain intensity (R=0.235, P=0.008; R=0.233, P=0.008). Moreover, a linear regression model showed interleukin-6 (IL-6), macrophage colony-stimulating factor 1 (CSF-1), FGF-21 and tumor necrosis factor superfamily member 12 (TWEAK) as significant independent parameters for pain intensity.

DISCUSSION: The associations between specific cytokines and KOA pain intensities provide new insights into the understanding of the underlying factors driving the pain in OA.