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Biomarkers in Osteoarthritis: Value of Proteomics

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Biomarkers in Bone Disease

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Abstract

Osteoarthritis (OA) is the most common rheumatic pathology accounting for much of worldwide disability. OA is related to aging and may affect the structure of any joint tissue. The early stage accurate diagnosis of OA and the ability to monitor the efficacy of putative disease-modifying drugs remain among the essential unmet medical needs for this disease. Despite the prevalence of OA, the diagnostic methods currently available are limited and lack sensitivity. Furthermore, there is currently no effective therapy capable of slowing or reversing the pathological changes that occur in the joint during the disease process. Therefore, the discovery and application of novel, noninvasive, specific biochemical markers remain a priority. This chapter will focus on the current OA protein markers and the value of proteomics for the discovery and validation of useful candidates for early diagnosis and drug discovery.

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Abbreviations

2-DE:

Two-dimensional gel electrophoresis

COL2:

Type II collagen

COMP:

Cartilage oligomeric matrix protein

CS:

Chondroitin sulfate

CTX-II:

C-telopeptide region of COL2

DIGE:

Differential in-gel electrophoresis

HA:

Hyaluronic acid

HC:

Healthy controls

iTRAQ:

Isobaric tag for relative quantitation

K/L:

Kellgren and Lawrence scale

KS:

Keratan sulfate

LC:

Liquid chromatography

MALDI-TOF/TOF:

Matrix-assisted laser desorption/ionization-time of flight

MB:

Magnetic beads

MMP:

Matrix metalloproteinases

MS:

Mass spectrometry

NAPPA:

Nucleic acid programmable protein array

OA:

Osteoarthritis

OARSI:

Osteoarthritis Research Society International

PAGE:

Polyacrylamide gel electrophoresis

PsA:

Psoriatic arthritis

RA:

Rheumatoid arthritis

SELDI:

Surface-enhanced laser desorption/ionization

SF:

Synovial fluid

SRM:

Selected reaction monitoring

TIMP:

Tissue inhibitor of matrix metalloproteinase

UF:

Ultrafiltration

YKL-40:

Cartilage glycoprotein 39

References

  • Aebersold R, Bader GD, Edwards AM, et al. The biology/disease-driven human proteome project (B/D-HPP): enabling protein research for the life sciences community. J Proteome Res. 2013;12(1):23–7.

    Article  CAS  PubMed  Google Scholar 

  • Aslam I, Perjar I, Shi XA, et al. Associations between biomarkers of joint metabolism, hand osteoarthritis, and hand pain and function: the Johnston County Osteoarthritis Project. J Rheumatol. 2014;41(5):938–44.

    Article  PubMed  PubMed Central  Google Scholar 

  • Balakrishnan L, Bhattacharjee M, Ahmad S, et al. Differential proteomic analysis of synovial fluid from rheumatoid arthritis and osteoarthritis patients. Clin Proteomics. 2014;11(1):1.

    Article  PubMed  PubMed Central  Google Scholar 

  • Bauer DC, Hunter DJ, Abramson SB, et al. Classification of osteoarthritis biomarkers: a proposed approach. Osteoarthritis Cartilage. 2006;14(8):723–7.

    Article  CAS  PubMed  Google Scholar 

  • Blanco FJ. Osteoarthritis year in review 2014: we need more biochemical biomarkers in qualification phase. Osteoarthritis Cartilage. 2014;22(12):2025–32.

    Article  PubMed  Google Scholar 

  • Bos SD, Beekman M, Maier AB, et al. Metabolic health in families enriched for longevity is associated with low prevalence of hand osteoarthritis and influences OA biomarker profiles. Ann Rheum Dis. 2013;72(10):1669–74.

    Article  PubMed  Google Scholar 

  • Chaganti RK, Kelman A, Lui L, et al. Change in serum measurements of cartilage oligomeric matrix protein and association with the development and worsening of radiographic hip osteoarthritis. Osteoarthritis Cartilage. 2008;16(5):566–71.

    Article  CAS  PubMed  Google Scholar 

  • Cretu D, Prassas I, Saraon P, et al. Identification of psoriatic arthritis mediators in synovial fluid by quantitative mass spectrometry. Clin Proteomics. 2014;11(1):27.

    Article  PubMed  PubMed Central  Google Scholar 

  • Davis CR, Karl J, Granell R, et al. Can biochemical markers serve as surrogates for imaging in knee osteoarthritis? Arthritis Rheum. 2007;56(12):4038–47.

    Article  CAS  PubMed  Google Scholar 

  • de Seny D, Fillet M, Meuwis MA, et al. Discovery of new rheumatoid arthritis biomarkers using the surface-enhanced laser desorption/ionization time-of-flight mass spectrometry ProteinChip approach. Arthritis Rheum. 2005;52(12):3801–12.

    Article  PubMed  Google Scholar 

  • de Seny D, Fillet M, Ribbens C, et al. Monomeric calgranulins measured by SELDI-TOF mass spectrometry and calprotectin measured by ELISA as biomarkers in arthritis. Clin Chem. 2008;54:1066.

    Article  PubMed  Google Scholar 

  • de Seny D, Sharif M, Fillet M, et al. Discovery and biochemical characterisation of four novel biomarkers for osteoarthritis. Ann Rheum Dis. 2011;70(6):1144–52.

    Article  PubMed  Google Scholar 

  • Drynda S, Ringel B, Kekow M, et al. Proteome analysis reveals disease-associated marker proteins to differentiate RA patients from other inflammatory joint diseases with the potential to monitor anti-TNFalpha therapy. Pathol Res Pract. 2004;200(2):165–71.

    Article  CAS  PubMed  Google Scholar 

  • Dufield DR, Nemirovskiy OV, Jennings MG, Tortorella MD, Malfait AM, Mathews WR. An immunoaffinity liquid chromatography-tandem mass spectrometry assay for detection of endogenous aggrecan fragments in biological fluids: use as a biomarker for aggrecanase activity and cartilage degradation. Anal Biochem. 2010;406(2):113–23.

    Article  CAS  PubMed  Google Scholar 

  • Fernandes FA, Pucinelli ML, da Silva NP, Feldman D. Serum cartilage oligomeric matrix protein (COMP) levels in knee osteoarthritis in a Brazilian population: clinical and radiological correlation. Scand J Rheumatol. 2007;36(3):211–5.

    Article  CAS  PubMed  Google Scholar 

  • Fernandez-Costa C, Calamia V, Fernandez-Puente P, Capelo-Martinez J-L, Ruiz-Romero C, Blanco FJ. Sequential depletion of human serum for the search of osteoarthritis biomarkers. Proteome Sci. 2012;10:55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fernandez-Puente P, Mateos J, Fernandez-Costa C, et al. Identification of a panel of novel serum osteoarthritis biomarkers. J Proteome Res. 2011;10(11):5095–101.

    Article  CAS  PubMed  Google Scholar 

  • Garnero P, Rousseau JC, Delmas PD. Molecular basis and clinical use of biochemical markers of bone, cartilage, and synovium in joint diseases. Arthritis Rheum. 2000;43(5):953–68.

    Article  CAS  PubMed  Google Scholar 

  • Gobezie R, Kho A, Krastins B, et al. High abundance synovial fluid proteome: distinct profiles in health and osteoarthritis. Arthritis Res Ther. 2007;9(2):R36.

    Article  PubMed  PubMed Central  Google Scholar 

  • Han MY, Dai JJ, Zhang Y, et al. Identification of osteoarthritis biomarkers by proteomic analysis of synovial fluid. J Int Med Res. 2012;40(6):2243–50.

    Article  CAS  PubMed  Google Scholar 

  • Henjes F, Lourido L, Ruiz-Romero C, et al. Analysis of autoantibody profiles in osteoarthritis using comprehensive protein array concepts. J Proteome Res. 2014;13(11):5218–29.

    Article  CAS  PubMed  Google Scholar 

  • Henrotin Y, Addison S, Kraus V, Deberg M. Type II collagen markers in osteoarthritis: what do they indicate? Curr Opin Rheumatol. 2007;19(5):444–50.

    Article  CAS  PubMed  Google Scholar 

  • Hoch JM, Mattacola CG, Medina McKeon JM, Howard JS, Lattermann C. Serum cartilage oligomeric matrix protein (sCOMP) is elevated in patients with knee osteoarthritis: a systematic review and meta-analysis. Osteoarthritis Cartilage. 2011;19(12):1396–404.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang K, Wu LD. YKL-40: a potential biomarker for osteoarthritis. J Int Med Res. 2009;37(1):18–24.

    Article  CAS  PubMed  Google Scholar 

  • Hui AY, McCarty WJ, Masuda K, Firestein GS, Sah RL. A systems biology approach to synovial joint lubrication in health, injury, and disease. Wiley Interdiscip Rev Syst Biol Med. 2012;4(1):15–37.

    Article  CAS  PubMed  Google Scholar 

  • Kamphorst J, van der Heijden R, DeGroot J, et al. Profiling of endogenous peptides in human synovial fluid by NanoLC-MS: method validation and peptide identification. J Proteome Res. 2007;6(11):4388–96.

    Article  CAS  PubMed  Google Scholar 

  • Kraus VB, Blanco FJ, Englund M, Karsdal MA, Lohmander LS. Call for standardized definitions of osteoarthritis and risk stratification for clinical trials and clinical use. Osteoarthritis Cartilage. 2015;23(8):1233–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lohmander LS, Ostenberg A, Englund M, Roos H. High prevalence of knee osteoarthritis, pain, and functional limitations in female soccer players twelve years after anterior cruciate ligament injury. Arthritis Rheum. 2004;50(10):3145–52.

    Article  CAS  PubMed  Google Scholar 

  • Lotz M, Martel-Pelletier J, Christiansen C, et al. Value of biomarkers in osteoarthritis: current status and perspectives. Ann Rheum Dis. 2013;72(11):1756–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mateos J, Lourido L, Fernández-Puente P, et al. Differential protein profiling of synovial fluid from rheumatoid arthritis and osteoarthritis patients using LC-MALDI TOF/TOF. J Proteomics. 2012;75(10):2869–78.

    Article  CAS  PubMed  Google Scholar 

  • Mazieres B, Hucher M, Zaim M, Garnero P. Effect of chondroitin sulphate in symptomatic knee osteoarthritis: a multicentre, randomised, double-blind, placebo-controlled study. Ann Rheum Dis. 2007;66(5):639–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McAlindon TE, Bannuru RR, Sullivan MC, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthritis Cartilage. 2014;22(3):363–88.

    Article  CAS  PubMed  Google Scholar 

  • Nemirovskiy OV, Dufield DR, Sunyer T, Aggarwal P, Welsch DJ, Mathews WR. Discovery and development of a type II collagen neoepitope (TIINE) biomarker for matrix metalloproteinase activity: from in vitro to in vivo. Anal Biochem. 2007;361(1):93–101.

    Article  CAS  PubMed  Google Scholar 

  • Olsen AK, Sondergaard BC, Byrjalsen I, et al. Anabolic and catabolic function of chondrocyte ex vivo is reflected by the metabolic processing of type II collagen. Osteoarthritis Cartilage. 2007;15(3):335–42.

    Article  CAS  PubMed  Google Scholar 

  • Pan X, Huang L, Chen J, Dai Y, Chen X. Analysis of synovial fluid in knee joint of osteoarthritis: 5 proteome patterns of joint inflammation based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Int Orthop. 2012;36(1):57–64.

    Article  PubMed  Google Scholar 

  • Raynauld JP, Martel-Pelletier J, Haraoui B, et al. Risk factors predictive of joint replacement in a 2-year multicentre clinical trial in knee osteoarthritis using MRI: results from over 6 years of observation. Ann Rheum Dis. 2011;70(8):1382–8.

    Article  PubMed  Google Scholar 

  • Reijman M, Hazes JM, Bierma-Zeinstra SM, et al. A new marker for osteoarthritis: cross-sectional and longitudinal approach. Arthritis Rheum. 2004;50(8):2471–8.

    Article  CAS  PubMed  Google Scholar 

  • Ritter SY, Subbaiah R, Bebek G, et al. Proteomic analysis of synovial fluid from the osteoarthritic knee: comparison with transcriptome analyses of joint tissues. Arthritis Rheum. 2013;65(4):981–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ritter SY, Collins J, Krastins B, et al. Mass spectrometry assays of plasma biomarkers to predict radiographic progression of knee osteoarthritis. Arthritis Res Ther. 2014;16(5):456.

    Article  PubMed  PubMed Central  Google Scholar 

  • Roos EM. Joint injury causes knee osteoarthritis in young adults. Curr Opin Rheumatol. 2005;17(2):195–200.

    Article  PubMed  Google Scholar 

  • Rousseau JC, Zhu Y, Miossec P, et al. Serum levels of type IIA procollagen amino terminal propeptide (PIIANP) are decreased in patients with knee osteoarthritis and rheumatoid arthritis. Osteoarthritis Cartilage. 2004;12(6):440–7.

    Article  PubMed  Google Scholar 

  • Ruiz-Romero C, Blanco FJ. The role of proteomics in osteoarthritis pathogenesis research. Curr Drug Targets. 2009;10(6):543–56.

    Article  CAS  PubMed  Google Scholar 

  • Ruiz-Romero C, Blanco FJ. Proteomics role in the search for improved diagnosis, prognosis and treatment of osteoarthritis. Osteoarthritis Cartilage. 2010;18(4):500–9.

    Article  CAS  PubMed  Google Scholar 

  • Ruiz-Romero C, Fernandez-Puente P, Calamia V, Blanco FJ. Lessons from the proteomic study of osteoarthritis. Expert Rev Proteomics. 2015;12(4):433–43.

    Article  CAS  PubMed  Google Scholar 

  • Sinz A, Bantscheff M, Mikkat S, et al. Mass spectrometric proteome analyses of synovial fluids and plasmas from patients suffering from rheumatoid arthritis and comparison to reactive arthritis or osteoarthritis. Electrophoresis. 2002;23(19):3445–56.

    Article  CAS  PubMed  Google Scholar 

  • Takinami Y, Yoshimatsu S, Uchiumi T, et al. Identification of potential prognostic markers for knee osteoarthritis by serum proteomic analysis. Biomark Insights. 2013;8:85–95.

    PubMed  PubMed Central  Google Scholar 

  • Uchida T, Fukawa A, Uchida M, Fujita K, Saito K. Application of a novel protein biochip technology for detection and identification of rheumatoid arthritis biomarkers in synovial fluid. J Proteome Res. 2002;1(6):495–9.

    Article  CAS  PubMed  Google Scholar 

  • Valdes AM, Van Oene M, Hart DJ, et al. Reproducible genetic associations between candidate genes and clinical knee osteoarthritis in men and women. Arthritis Rheum. 2006;54(2):533–9.

    Article  CAS  PubMed  Google Scholar 

  • Valdes AM, Meulenbelt I, Chassaing E, et al. Large scale meta-analysis of urinary C-terminal telopeptide, serum cartilage oligomeric protein and matrix metalloprotease degraded type II collagen and their role in prevalence, incidence and progression of osteoarthritis. Osteoarthritis Cartilage. 2014;22(5):683–9.

    Article  CAS  PubMed  Google Scholar 

  • van Spil WE, Drossaers-Bakker KW, Lafeber FP. Associations of CTX-II with biochemical markers of bone turnover raise questions on its tissue origin: data from CHECK, a cohort study of early osteoarthritis. Ann Rheum Dis. 2013;72(1):29–36.

    Article  PubMed  Google Scholar 

  • Yavin EJ, Preciado-Patt L, Rosen O, et al. Serum amyloid A-derived peptides, present in human rheumatic synovial fluids, induce the secretion of interferon-gamma by human CD(4)(+) T-lymphocytes. FEBS Lett. 2000;472(2–3):259–62.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Grupo de Proteómica, ProteoRed-PRB2/ISCIII, Servicio de Reumatología. Instituto de Investigación Biomédica (INIBIC). Complexo Hospitalario Universitario A Coruña (CHUAC). Sergas. Universidad de A Coruña (UDC), A Coruña, Spain

    Cristina Ruiz-Romero, Patricia Fernández-Puente & Francisco J. Blanco

  2. Rheumatology Divison, INIBIC-Hospital Universitario A Coruña, Xubias 84, 15006, A Coruña, Spain

    Francisco J. Blanco

  3. Proteomics Unit, INIBIC-Hospital Universitario A Coruña, Xubias 84, 15006, A Coruña, Spain

    Cristina Ruiz-Romero

Authors
  1. Cristina Ruiz-Romero
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  2. Patricia Fernández-Puente
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  3. Francisco J. Blanco
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Corresponding authors

Correspondence to Cristina Ruiz-Romero , Patricia Fernández-Puente or Francisco J. Blanco .

Editor information

Editors and Affiliations

  1. Sciences Division, King's College, London, United Kingdom

    Victor R. Preedy

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Ruiz-Romero, C., Fernández-Puente, P., Blanco, F.J. (2016). Biomarkers in Osteoarthritis: Value of Proteomics. In: Preedy, V. (eds) Biomarkers in Bone Disease. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7745-3_44-1

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  • DOI: https://doi.org/10.1007/978-94-007-7745-3_44-1

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  • Online ISBN: 978-94-007-7745-3

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