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Identification of plasma and urinary inflammatory markers in severe knee osteoarthritis: Relations with synovial fluid markers

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Background: This study aimed to identify plasma and urinary cytokines as potential biomarkers for severe knee osteoarthritis (OA). It also investigated associations between these cytokines and cartilage markers, as well as their connections with synovial fluid (SF) markers. Methods: Samples of plasma, urine, and SF were obtained from patients (n=40) undergoing total knee arthroplasty (TKA) or unicompartmental knee arthroplasty (UKA) due to severe knee OA. Control samples of plasma and urine were collected from non-OA individuals (n=15). We used a Luminex immunoassay for the simultaneous measurement of 19 cytokines, MMP-1, and MMP-3 levels. COMP, CTX-Ⅱ, and hyaluronan (HA) levels were quantified using Enzyme-linked immunosorbent assay (ELISA) kits. Receiver operating characteristic (ROC) curves were utilized to analyze each biomarker's performance. Correlations among these biomarkers were evaluated via Spearman’s correlation. Results: The levels of plasma (p)CCL11, pCXCL16, pIL-8, pIL-15, pHA, urinary (u)CCL2, uCCL11, uCCL19, uCXCL16, uIL-1β, uIL-6, uIL-8, uIL-12p70, uIL-15, uIL-33, uMMP-3, uHA, uCTX-II, and uCOMP were significantly elevated in individuals with severe knee OA. Notably, specific correlations were observed between the plasma/urine biomarkers and SF biomarkers: pCCL11 with sfHA (r=0.56) and sfTNF-α (r=0.58), pIL-15 with sfCCL19 (r=0.43) and sfCCL20 (r=0.44), and uCCL19 with sfCCL11 (r=0.45) and sfIL-33 (r=0.51). Positive correlations were also observed between uCCL11 and its corresponding sfCCL11(r=0.49), as well as between sfCCL11 and other cytokines, namely sfCCL4, sfCCL19, sfCCL20, sfIL-33, and sfTNF-α (r=0.46-0.63). Conclusion: This study provides an extensive profile of systemic inflammatory mediators in plasma of knee OA and identified four inflammatory markers (pCCL11, pIL-15, uCCL11 uCCL19) reflecting joint inflammation.

Abstract

Background: This study aimed to identify plasma and urinary cytokines as potential biomarkers for severe knee osteoarthritis (OA). It also investigated associations between these cytokines and cartilage markers, as well as their connections with synovial fluid (SF) markers. Methods: Samples of plasma, urine, and SF were obtained from patients (n=40) undergoing total knee arthroplasty (TKA) or unicompartmental knee arthroplasty (UKA) due to severe knee OA. Control samples of plasma and urine were collected from non-OA individuals (n=15). We used a Luminex immunoassay for the simultaneous measurement of 19 cytokines, MMP-1, and MMP-3 levels. COMP, CTX-Ⅱ, and hyaluronan (HA) levels were quantified using Enzyme-linked immunosorbent assay (ELISA) kits. Receiver operating characteristic (ROC) curves were utilized to analyze each biomarker's performance. Correlations among these biomarkers were evaluated via Spearman’s correlation. Results: The levels of plasma (p)CCL11, pCXCL16, pIL-8, pIL-15, pHA, urinary (u)CCL2, uCCL11, uCCL19, uCXCL16, uIL-1β, uIL-6, uIL-8, uIL-12p70, uIL-15, uIL-33, uMMP-3, uHA, uCTX-II, and uCOMP were significantly elevated in individuals with severe knee OA. Notably, specific correlations were observed between the plasma/urine biomarkers and SF biomarkers: pCCL11 with sfHA (r=0.56) and sfTNF-α (r=0.58), pIL-15 with sfCCL19 (r=0.43) and sfCCL20 (r=0.44), and uCCL19 with sfCCL11 (r=0.45) and sfIL-33 (r=0.51). Positive correlations were also observed between uCCL11 and its corresponding sfCCL11(r=0.49), as well as between sfCCL11 and other cytokines, namely sfCCL4, sfCCL19, sfCCL20, sfIL-33, and sfTNF-α (r=0.46-0.63). Conclusion: This study provides an extensive profile of systemic inflammatory mediators in plasma of knee OA and identified four inflammatory markers (pCCL11, pIL-15, uCCL11 uCCL19) reflecting joint inflammation.

참고문헌 (37)

  1. Meehan RT, "Synovial fluid cytokines, chemokines and MMP levels in osteoarthritis patients with knee pain display a profile similar to many rheumatoid arthritis patients", J Clin Med, 10(21), pp.5027~ (2021)[DOI]
  2. Mabey T, "Cytokines as biochemical markers for knee osteoarthritis", World J Orthop, 6(1), pp.95~105 (2015)[DOI]
  3. van Spil WE, "Osteoarthritis year in review 2019 : biomarkers(biochemical markers)", Osteoarthr Cartil, 28(3), pp.296~315 (2020)[DOI]
  4. Kraus VB, "Call for standardized definitions of osteoarthritis and risk stratification for clinical trials and clinical use", Osteoarthr Cartil, 23(8), pp.1233~1241 (2015)[DOI]
  5. de Lange-Brokaar BJ, "Synovial inflammation, immune cells and their cytokines in osteoarthritis : a review", Osteoarthr Cartil, 20(12), pp.1484~1499 (2012)[DOI]
  6. Atukorala I, "Synovitis in knee osteoarthritis : a precursor of disease?", Ann Rheum Dis, 75(2), pp.390~395 (2016)[DOI]
  7. Kisand K, "New insights into the natural course of knee osteoarthritis: early regulation of cytokines and growth factors, with emphasis on sex-dependent angiogenesis and tissue remodeling. A pilot study", Osteoarthr Cartil, 26(8), pp.1045~1054 (2018)[DOI]
  8. Yang CR, "Denbinobin upregulates miR-146a expression and attenuates IL-1beta-induced upregulation of ICAM-1 and VCAM-1 expressions in osteoarthritis fibroblast-like synoviocytes", J Mol Med, 92(11), pp.1147~1158 (2014)[DOI]
  9. Benito MJ, "Synovial tissue inflammation in early and late osteoarthritis", Ann Rheum Dis, 64(9), pp.1263~1267 (2005)[DOI]
  10. Koskinen A, "Resistin as a factor in osteoarthritis : synovial fluid resistin concentrations correlate positively with interleukin 6 and matrix metalloproteinases MMP-1 and MMP-3", Scand J Rheumatol, 43(3), pp.249~253 (2014)[DOI]
  11. Braaten JA, "Biomarkers for osteoarthritis diseases", Life, 12(11), pp.1799~ (2022)
  12. Rousseau JC, "Soluble biological markers in osteoarthritis", Ther Adv Musculoskelet Dis (2021)[DOI]
  13. Boffa A, "Synovial fluid biomarkers in knee osteoarthritis : a systematic review and quantitative evaluation using BIPEDs criteria", Cartilage, 13(1), pp.82S~103S (2021)[DOI]
  14. Scanzello CR, "Chemokines and inflammation in osteoarthritis : insights from patients and animal models", J Orthop Res, 35(4), pp.735~739 (2017)[DOI]
  15. Clarke J, "IL-33 is a potential new target in OA", Nat Rev Rheumatol, 17(1), pp.3~ (2021)[DOI]
  16. Barbu C, "Inflammation in COPD : pathogenesis, local and systemic effects", Rom J Morphol Embryol, 52(1), pp.21~27 (2011)
  17. Scott DL, "Rheumatoid arthritis", Lancet, 376(9746), pp.1094~1108 (2010)[DOI]
  18. Aregay A, "Systemic inflammation and immune cell phenotypes are associated with neuro-psychiatric symptoms in patients with chronic inflammatory liver diseases", Liver Int, 38(12), pp.2317~2328 (2018)[DOI]
  19. Li H, "Causal effects of systemic inflammatory regulators on chronic kidney diseases and renal function : a bidirectional Mendelian randomization study", Front Immunol, 14, pp.1229636~ (2023)[DOI]
  20. Rohm TV, "Inflammation in obesity, diabetes, and related disorders", Immunity, 55(1), pp.31~55 (2022)[DOI]
  21. Muzes G, "Changes of the cytokine profile in inflammatory bowel diseases", World J Gastroenterol, 18(41), pp.5848~5861 (2012)[DOI]
  22. Kiss M, "Systemic reprogramming of monocytes in cancer", Front Oncol (2020)[DOI]
  23. Altman R, "Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee", Arthritis Rheum, 29(8), pp.1039~1049 (1986), Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association[DOI]
  24. Jayadev C, "Hyaluronidase treatment of synovial fluid to improve assay precision for biomarker research using multiplex immunoassay platforms", J Immunol Methods, 386(1–2), pp.22~30 (2012)[DOI]
  25. Cheng H, "C-terminal cross-linked telopeptides of type II collagen as biomarker for radiological knee osteoarthritis : a meta-analysis", Cartilage, 11(4), pp.512~520 (2020)[DOI]
  26. Liem Y, "Biochemical, clinical, demographic and imaging biomarkers for disease progression in knee osteoarthritis", Biomark Med, 16(8), pp.633~645 (2022)[DOI]
  27. Jung M, "Increased urinary concentration of collagen type II C-telopeptide fragments in patients with osteoarthritis", Pathobiology, 71(2), pp.70~76 (2004)[DOI]
  28. Kraus VB, "Predictive validity of biochemical biomarkers in knee osteoarthritis : data from the FNIH OA Biomarkers Consortium", Ann Rheum Dis, 76(1), pp.186~195 (2017)[DOI]
  29. Hsu YH, "Production of the chemokine eotaxin-1 in osteoarthritis and its role in cartilage degradation", J Cell Biochem, 93(5), pp.929~939 (2004)[DOI]
  30. Li B, "Synovial fluid eotaxin-1 levels may reflect disease progression in primary knee osteoarthritis among elderly Han Chinese : a cross-sectional study", Cartilage, 10(4), pp.408~416 (2019)[DOI]
  31. Chao PZ, "Regulation of MMP-3 expression and secretion by the chemokine eotaxin-1 in human chondrocytes", J Biomed Sci, 18(1), pp.86~ (2011)[DOI]
  32. Galicia K, "Inflammatory biomarker profiling in total joint arthroplasty and its relevance to circulating levels of lubricin, a novel proteoglycan", Clin Appl Thromb Hemost, 24(6), pp.950~959 (2018)[DOI]
  33. Ruan G, "Correction to : associations between serumIL-8 and knee symptoms, joint structures, and cartilage or bone biomarkers in patients with knee osteoarthritis", Clin Rheumatol, 39(7), pp.2249~ (2020)[DOI]
  34. Koh SM, "Elevated plasma and synovial fluid interleukin-8 and interleukin-18 may be associated with the pathogenesis of knee osteoarthritis", Knee, 27(1), pp.26~35 (2020)[DOI]
  35. Sun JM, "Serum interleukin-15 levels are associated with severity of pain in patients with knee osteoarthritis", Dis Markers, 35(3), pp.203~206 (2013)[DOI]
  36. Scanzello CR, "Local cytokine profiles in knee osteoarthritis : elevated synovial fluid interleukin-15 differentiates early from end-stage disease", Osteoarthr Cartil, 17(8), pp.1040~1048 (2009)[DOI]
  37. Sokolove J, "Role of inflammation in the pathogenesis of osteoarthritis : latest findings and interpretations", Ther Adv Musculoskelet Dis, 5(2), pp.77~94 (2013)[DOI]

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