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; pain was assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Neuropathic Pain Questionnaire (NPQ). Linear regression was used to investigate associations between biomarkers and synovitis, and biomarkers and pain while controlling for age, sex, and body mass index. We also tested whether associations between biomarkers and pain were confounded by synovitis. We found sf-IL-6 was associated with synovitis in the parapatellar subregion (B = 0.006; 95% confidence interval [CI] 0.003-0.010), and no association between p-IL-6 and synovitis. We also observed an association between C1M and synovitis in the periligamentous subregion (B = 0.013; 95% CI 0.003-0.023). Furthermore, sf-IL-6, but not p-IL-6, was significantly associated with pain, WOMAC (B = 0.022; 95% CI 0.004-0.040), and NPQ (B = 0.043; 95% CI 0.005-0.082). There was no association between C1M and WOMAC pain, but we did find an association between C1M and NPQ (B = 0.229; 95% CI 0.036-0.422). Lastly, synovitis explained both biomarker-NPQ associations, 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.
Nordic Bioscience Biomarkers & Research, Nordic Bioscience A/S, Herlev, Denmark.|Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Maja R
MR
Radojčić
Nordic Bioscience Biomarkers & Research, Nordic Bioscience A/S, Herlev, Denmark.
Christian S
CS
Thudium
Nordic Bioscience Biomarkers & Research, Nordic Bioscience A/S, Herlev, Denmark.
Kim
K
Henriksen
Neuroscience, Innovative Medicines and Early Development, AstraZeneca, Cambridge, United Kingdom.
Keith
K
Tan
Department of Surgical Sciences, Anaesthesiology and Intensive Care, Uppsala University, Uppsala, Sweden.
Rolf
R
Karlsten
Neuroscience, Innovative Medicines and Early Development, AstraZeneca, Cambridge, United Kingdom.
Amanda
A
Dudley
Neuroscience, Innovative Medicines and Early Development, AstraZeneca, Cambridge, United Kingdom.
Iain
I
Chessell
Nordic Bioscience Biomarkers & Research, Nordic Bioscience A/S, Herlev, Denmark.
Morten A
MA
Karsdal
Nordic Bioscience Biomarkers & Research, Nordic Bioscience A/S, Herlev, Denmark.
Anne-Christine
AC
Bay-Jensen
Quantitative Imaging Center, Department of Radiology, Boston University School of Medicine, Boston, MA, USA.|Department of Radiology, Hôpital Saint-Antoine, University Paris VI, Paris, France.
Michel D
MD
Crema
Quantitative Imaging Center, Department of Radiology, Boston University School of Medicine, Boston, MA, USA.
Ali
A
Guermazi
D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism*; D007719:Knee Joint / Q000000981:diagnostic imaging / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging / Q000378:metabolism*; D010147:Pain Measurement; D013582:Synovial Fluid / Q000378:metabolism*; D013585:Synovitis / Q000000981:diagnostic imaging / Q000378:metabolism
D015415:Biomarkers; D015850:Interleukin-6