Biomarker of extracellular matrix remodelling C1M and proinflammatory cytokine interleukin 6 are related to synovitis and pain in end-stage knee osteoarthritis patients

Little is known about local and systemic biomarkers in relation to synovitis and pain in end-stage osteoarthritis (OA) patients. We investigated the associations between the novel extracellular matrix biomarker, C1M, and local and systemic interleukin 6 (IL-6) with synovitis and pain. Serum C1M, plasma, and synovial fluid IL-6 (p-IL-6, sf-IL-6) were measured in 104 end-stage knee OA patients. Contrast-enhanced magnetic resonance imaging was used to semiquantitatively assess an 11-point synovitis score; painwas assessed by theWesternOntario and McMaster Universities Osteoarthritis Index (WOMAC) and the Neuropathic PainQuestionnaire (NPQ). Linear regression was used to investigate associations between biomarkers and synovitis, and biomarkers and pain while controlling for age, sex, and bodymass index. We also testedwhether associations between biomarkers and painwere confounded by synovitis. We found sf-IL-6 was associated with synovitis in the parapatellar subregion (B 5 0.006; 95% confidence interval [ CI] 0.003-0.010), and no association between p-IL-6 and synovitis. We also observed an association betweenC1Mand synovitis in the periligamentous subregion (B50.013; 95% CI 0.003-0.023). Furthermore, sf-IL-6, but not p-IL-6, was significantly associated with pain, WOMAC(B50.022; 95% CI 0.004-0.040), andNPQ(B50.043; 95% CI 0.005-0.082). Therewas no association betweenC1MandWOMACpain, butwe did find an association between C1M and NPQ (B50.229; 95% CI 0.036-0.422). Lastly, synovitis explained both biomarker-NPQassociations, but not the biomarker-WOMAC association. These results suggest that C1M and IL-6 are associated with synovitis and pain, and synovitis is an important confounding variable when studying biomarkers and neuropathic features in OA patients.