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Cartilage oligomeric protein, matrix metalloproteinase-3, and Coll2-1 as serum biomarkers in knee osteoarthritis: a cross-sectional study

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Abstract

Biochemical markers reflecting joint remodeling in osteoarthritis (OA) are a promising diagnostic tool. The aim of this study was to investigate serum levels of candidate biomarkers in subjects with and without knee OA and assess their correlation with clinical parameters and knee structural damage. 56 patients with primary knee OA and 31 healthy controls participated in this study. Patients were separated into two groups: isolated knee OA and generalized OA. Clinical parameters were obtained by validated self-reported questionnaires and a visual analogue scale. Serum levels of cartilage oligomeric protein (COMP), matrix metalloproteinase-3 (MMP-3), and Coll2-1 were quantified by enzyme-linked immunosorbent assay. Knee structural damage was determined by plain X-ray and 1.5 T magnetic resonance imaging (MRI), using Kellgren–Lawrence (KL) grading scale and Whole-Organ Magnetic Resonance Imaging Score (WORMS), respectively. Compared to controls, patients had significantly higher median serum COMP (985 vs. 625 ng/ml; p < 0.001) and MMP-3 (36.85 vs. 22.10 ng/ml; p = 0.003) levels. Patients with radiographic evidence of KLII/III knee OA had greater median COMP levels than KLI patients (1095 vs. 720 ng/ml; p = 0.001). In the generalized OA group, mean MMP-3 levels were higher than in the isolated knee OA group (30.40 vs. 55.13 ng/ml; p < 0.001). COMP correlated positively with WORMS (r s = 0.454, p < 0.001) and MMP-3 (r s = 0.337, p = 0.003). Cut-off values for serum COMP and MMP-3 were determined. We observed higher serum COMP and MMP-3 levels in knee OA patients compared to controls. COMP may reflect knee structural damage, while MMP-3—OA “generalization”.

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References

  1. Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, Christy W, Cooke TD, Greenwald R, Hochberg M, Howell D, Kaplan D, Koopman W, Longley S III, Mankin H, McShane DJ, Medsger T Jr, Meenan R, Mikkelsen W, Moskowitz R, Murphy W, Rothschild B, Segal M, Sokoloff L, Wolfe F (1986) Development of criteria for the classification and reporting of osteoarthritis: classification of osteoarthritis of the knee. Arthritis Rheumatol 29(8):1039–1049

    Article  CAS  Google Scholar 

  2. Hart DJ, Spector TD, Brown P, Wilson P, Doyle DV, Silman AJ (1991) Clinical signs of early osteoarthritis: reproducibility and relation to X-ray changes in 541 women in the general population. Ann Rheum Dis 50(7):467–470

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Biomarkers Definitions Working Group (2001) Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework. Clin Pharmacol Ther 69: 89–95

    Article  Google Scholar 

  4. Eckstein F, Burstein D, Link TM (2006) Quantitative MRI of cartilage and bone: degenerative changes in osteoarthritis. NMR Biomed 19(7):822–854

    Article  PubMed  Google Scholar 

  5. Pelletier JP, Cooper C, Peterfy C, Reginster JY, Brandi ML, Bruyère O, Chapurlat R et al (2013) What is the predictive value of MRI for the occurrence of knee replacement surgery in knee osteoarthritis? Ann Rheum Dis 72(10):1594–1604

    Article  PubMed  Google Scholar 

  6. Kraus VB, Burnett B, Coindreau J et al (2011) Application of biomarkers in the development of drugs intended for the treatment of osteoarthritis. Osteoarthr Cartil 19(5):515–542

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Lotz M, Martel-Pelletier J, Christiansen C, Brandi ML, Bruyère O, Chapurlat R, Collette J et al (2013) Value of biomarkers in osteoarthritis: current status and perspectives. Ann Rheum Dis 72(11):1756–1763

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Georgiev TA, Stoilov R, Ivanova M (2013) Biomarkers in osteoarthritis. Revmatologiia 21(4):21–25

    Google Scholar 

  9. Smith RKW, Heinegård D (2000) Cartilage oligomeric matrix protein (COMP) levels in digital sheath synovial fluid and serum with tendon injury. Equine Vet J 32(1):52–58

    Article  CAS  PubMed  Google Scholar 

  10. Bauer DC, Hunter DJ, Abramson SB et al (2006) Classification of osteoarthritis biomarkers: a proposed approach. Osteoarthr Cartil 14(8):723–727

    Article  CAS  PubMed  Google Scholar 

  11. Rousseau JC, Garnero P (2012) Biological markers in osteoarthritis. Bone 51(2):265–277

    Article  CAS  PubMed  Google Scholar 

  12. Bruyere O, Collette J, Kothari M et al (2006) Osteoarthritis, magnetic resonance imaging, and biochemical markers: a one year prospective study. Ann Rheum Dis 65:1050–1054

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Vilım V, Olejarova M, Macháček S, Gatterova J, Kraus VB, Pavelka K (2002) Serum levels of cartilage oligomeric matrix protein (COMP) correlate with radiographic progression of knee osteoarthritis. Osteoarthr Cartil 10(9):707–713

    Article  PubMed  Google Scholar 

  14. Singh S, Shahi U, Kumar D, Shahi NT (2014) Serum Cartilage Oligomeric Matrix Protein: Tool for early diagnosis and grading of severity of primary knee osteoarthritis. Int J Osteol Orthop 1:1–7

    Google Scholar 

  15. Awadallah AM, Gehan HS, Tarek MK (2010) Serum level of cartilage oligomeric matrix protein as a screening modality for osteoarthritis among knee joint pain patients. J Am Sci 6(12)

  16. Clark AG, Jordan JM, Vilim V, Renner JB, Dragomir AD, Luta G, Kraus VB (1999) Serum cartilage oligomeric matrix protein reflects osteoarthritis presence and severity: the Johnston County Osteoarthritis Project. Arthritis Rheumatol 42(11):2356–2364

    Article  CAS  Google Scholar 

  17. Ribbens CY, Porras MM, Franchimont N et al (2002) Increased matrix metalloproteinase-3 serum levels in rheumatic diseases: relationship with synovitis and steroid treatment. Ann Rheum Dis 61(2):161–166

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kopchev A, Monov S, Kyurkchiev D, Ivanova I, Georgiev T (2017) Vascular endothelial growth factor (VEGF), cartilage oligomeric protein (COMP) and matrix metalloproteinase 3 (MMP-3) as serum biomarkers in psoriatic arthritis. Int J Pharm Sci Inven 6(7):08–12

    Google Scholar 

  19. Connelly AE, Tucker AJ, Kott LS, Duncan AM, Wright AJ (2014) Serum biochemical markers of joint metabolism and inflammation in relation to clinical symptoms and physical function in adults with symptomatic knee osteoarthritis. Osteoarthr Cartil 22:S66

    Article  Google Scholar 

  20. Li W, Du C, Wang H, Zhang C (2014) Increased serum ADAMTS-4 in knee osteoarthritis: a potential indicator for the diagnosis of osteoarthritis in early stages. Genet Mol Res 13(4):9642–9649

    Article  CAS  PubMed  Google Scholar 

  21. Pelletier J, Raynauld J, Caron J, Mineau F, Abram F, Dorais M et al (2010) Decrease in serum level of matrix metalloproteinases is predictive of the disease-modifying effect of osteoarthritis drugs assessed by quantitative MRI in patients with knee osteoarthritis. Ann Rheum Dis 69(12):2095–2101

    Article  CAS  PubMed  Google Scholar 

  22. Deberg M, Labasse A, Christgau S, Cloos P et al (2005) New serum biochemical markers (Coll 2-1 and Coll 2-1 NO 2) for studying oxidative-related type II collagen network degradation in patients with osteoarthritis and rheumatoid arthritis. Osteoarthr Cartil 13(3):258–265

    Article  PubMed  Google Scholar 

  23. Henrotin Y, Conrozier T, Deberg M, Walliser-Lohse A, Richette P, Mulleman D et al (2013) Early decrease of serum biomarkers of type II collagen degradation (Coll2-1) and joint inflammation (Coll2-1 NO2) by hyaluronic acid intra-articular injections in patients with knee osteoarthritis: A research study part of the Biovisco study. J Orthop Res 31(6):901–907

    Article  CAS  PubMed  Google Scholar 

  24. Deberg MA, Labasse AH, Collette J, Seidel L, Reginster JY, Henrotin YE (2005) One-year increase of Coll 2-1, a new marker of type II collagen degradation, in urine is highly predictive of radiological OA progression. Osteoarthr Cartil 13:1059–1065

    Article  CAS  PubMed  Google Scholar 

  25. Lequesne MG, Mery C, Samson M, Gerard P (1987) Indexes of severity for osteoarthritis of the hip and knee. Validation–value in comparison with other assessment tests. Scand J Rheumatol Suppl 65:85–89

    Article  CAS  PubMed  Google Scholar 

  26. Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW (1988) Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol 15:1833–1840

    CAS  PubMed  Google Scholar 

  27. Kellgren JH, Lawrence JS (1957) Radiological assessment of osteo-arthrosis. Ann Rheum Dis 16:494–502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Peterfy CG, Guermazi A, Zaim S et al (2004) Whole-organ magnetic resonance imaging score (WORMS) of the knee in osteoarthritis. Osteoarthr Cartil 12(3):177–190

    Article  CAS  PubMed  Google Scholar 

  29. Schiphof D, Boers M, Bierma-Zeinstra SM (2008) Differences in descriptions of Kellgren and Lawrence grades of knee osteoarthritis. Ann Rheum Dis 67(7):1034–1036

    Article  CAS  PubMed  Google Scholar 

  30. Verma P, Dalal K (2013) Serum cartilage oligomeric matrix protein (COMP) in knee osteoarthritis: a novel diagnostic and prognostic biomarker. J Orthop Res 31(7):999–1006

    Article  CAS  PubMed  Google Scholar 

  31. Naito К, Takahashi М, Kushida К, Suzuki М, Ohishi Т, Miura М, Inoue Т, Nagano А (1999) Measurement of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in patients with knee osteoarthritis: comparison with generalized osteoarthritis. Rheumatology 38(6):510–515

    Article  CAS  PubMed  Google Scholar 

  32. Recht MP, Kramer J, Marcelis S, Pathria MN et al (1993) Abnormalities of articular cartilage in the knee: analysis of available MR techniques. Radiology 187:473–478

    Article  CAS  PubMed  Google Scholar 

  33. Rifai N, Paul MR (2001) High-sensitivity C-reactive protein: a novel and promising marker of coronary heart disease. Clin Chem 47(3):403–411

    CAS  PubMed  Google Scholar 

  34. Danesh J, Wheeler JG, Hirschfield GM, Eda S et al (2004) C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. N Engl J Med 350(14):1387–1397

    Article  CAS  PubMed  Google Scholar 

  35. Pearson TA, Mensah GA, Alexander RW et al (2003) Markers of inflammation and cardiovascular disease. Circulation 107(3):499–511

    Article  PubMed  Google Scholar 

  36. Pearle AD, Scanzello CR, George S et al (2007) Elevated high-sensitivity C-reactive protein levels are associated with local inflammatory findings in patients with osteoarthritis. Osteoarthr Cartil 15(5):516–523

    Article  CAS  PubMed  Google Scholar 

  37. Miller ME, Rejeski WJ, Messier SP et al (2001) Modifiers of change in physical functioning in older adults with knee pain: the Observational Arthritis Study in Seniors (OASIS). Arthritis Rheum 45:331–339

    Article  CAS  PubMed  Google Scholar 

  38. Bedson J, Croft PR (2008) The discordance between clinical and radiographic knee osteoarthritis: a systematic search and summary of the literature. BMC Musculoskelet Disord 9:116

    Article  PubMed  PubMed Central  Google Scholar 

  39. Stoilov R, Ivanova M, Garbeva K, Marinova N, Manolova I, Kalitchin Z (2011) Evaluation of lubrication and friction in knee joint attacked by osteoarthritis treated with ostenil, ostenil plus, yaral forte and durolane. J Balk Tribol Assoc 17(3):456–461

    CAS  Google Scholar 

  40. Felson DT, Naimark A, Anderson J, Kazis L, Castelli W, Meenan RF (1987) The prevalence of knee osteoarthritis in the elderly. Fram Osteoarthr Study Arthritis Rheumatol 30(8):914–918

    Article  CAS  Google Scholar 

  41. Anderson АS, Richard FL (2010) Why is osteoarthritis an age-related disease? Best Pract Res Clin Rheumatol 24(1):15–26

    Article  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Clinic of Rheumatology, University Hospital “St. Ivan Rilski”, Medical Faculty, Medical University of Sofia, Sofia, Bulgaria

    Tsvetoslav Georgiev, Mariana Ivanova, Aleksandar Kopchev, Rasho Rashkov & Rumen Stoilov

  2. Laboratory of Clinical Immunology, University Hospital “Lozenets”, Medical Faculty, Sofia University, Sofia, Bulgaria

    Tsvetelina Velikova

  3. Radiology Department, University Hospital “St. Ivan Rilski”, Sofia, Bulgaria

    Asen Miloshov & Marin Penkov

  4. Laboratory of Clinical Immunology, University Hospital “St. Ivan Rilski”, Medical Faculty, Medical University of Sofia, Sofia, Bulgaria

    Ekaterina Kurteva & Kalina Yuzeir

  5. Clinic of Endocrinology, University Hospital “Aleksandrovska”, Medical Faculty, Medical University of Sofia, Sofia, Bulgaria

    Plamena Kabakchieva

Authors
  1. Tsvetoslav Georgiev
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  2. Mariana Ivanova
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  4. Tsvetelina Velikova
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Contributions

TG participated in constructing the idea behind this manuscript, executing the experiments, data management, analysis and reporting, logical interpretation, and presentation of the results. MI and AK took part in statistical analysis, logical interpretation and presentation of the results and in planning the methodology to reach the conclusion. AM and MP did an excellent work at designing and collecting the necessary data concerning the imaging modalities. Patient data collection and processing of relevant information was PK’s main task. TV, EK and KY carried out the immunoassays for detection of biomarkers. RR and RS organized and supervised the course of the work, which ended with reviewing the article before submission for its intellectual content. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Tsvetoslav Georgiev.

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Ethical standards

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.

Informed consent

Informed consent was obtained from all patients for being included in the study.

Funding

This work was supported by the Medical University of Sofia under project “Young Investigator” no 353/2015, contract no 22-D/2015.

Conflict of interest

The authors declare that there is no conflict of interest regarding the publication of this article.

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Georgiev, T., Ivanova, M., Kopchev, A. et al. Cartilage oligomeric protein, matrix metalloproteinase-3, and Coll2-1 as serum biomarkers in knee osteoarthritis: a cross-sectional study. Rheumatol Int 38, 821–830 (2018). https://doi.org/10.1007/s00296-017-3887-y

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