Skip to main content

Advertisement

Log in

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

  • Original Paper
  • Published:
International Orthopaedics Aims and scope Submit manuscript

Abstract

Purpose

The purpose of this study was to use matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) in osteoarthritis research. Our aim was to find differentially expressed disease-related and condition-specific peptide in synovial fluid in the knee joint of patients suffering from osteoarthritis (OA), and to develop and validate the peptide classification model for OA diagnosis.

Methods

Based on the American College of Rheumatology criteria, 30 OA cases and ten healthy donors were enrolled and underwent analysis. Magnetic beads-based weak cation exchange chromatography (MB-WCX) was performed for sample processing, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was conducted for peptide profile. ClinProt software 2.2 was used for data analysis and a genetic algorithm was created for class prediction.

Results

Two peptide peaks were found which may be characterised as the potential diagnostic markers for OA. Two other significantly different peptide peaks were found in OA patients at a medium stage compared to the early and late stages. A genetic algorithm (GA) was used to establish differential diagnosis models of OA. As a result, the algorithm models marked 100% of OA, and of 97.92% of medium-stage OA.

Conclusion

This study demonstrated that use of proteomics methods to identify potential biomarkers of OA is possible, and the identified potential biomarkers may be potential markers for diagnosis and monitoring the progression of OA.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Ding C, Garnero P, Cicuttini F, Scott F, Cooley H, Jones G (2005) Knee cartilage defects: association with early radiographic osteoarthritis, decreased cartilage volume, increased joint surface area and type II collagen breakdown. Osteoarthritis Cartilage 13(3):198–205

    Article  PubMed  Google Scholar 

  2. Conaghan PG, Felson D, Gold G, Lohmander S, Totterman S, Altman R (2006) MRI and non-cartilaginous structures in knee osteoarthritis. Osteoarthritis Cartilage 14(SupplA):A87–94

    Google Scholar 

  3. Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA et al (2008) Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis Rheum 58:26–35

    Article  PubMed  Google Scholar 

  4. Kang X, Fransen M, Zhang Y, Li H, Ke Y, Lu M et al (2009) The high prevalence of knee osteoarthritis in a rural Chinese population: the Wuchuan osteoarthritis study. Arthritis Rheum 61(5):641–647

    Article  PubMed  Google Scholar 

  5. Williams F, Spector T (2008) Biomarkers in osteoarthritis. Arthritis Res Ther 10(1):101

    Article  PubMed  Google Scholar 

  6. Gobezie R, Kho A, Krastins B, Sarracino DA, Thornhill TS, Chase M, Millett PJ, Lee DM (2007) High abundance synovial fluid proteome: distinct profiles in health and osteoarthritis. Arthritis Res Ther 9(2):R36

    Article  PubMed  Google Scholar 

  7. Rousseau JC, Delmas DPD (2007) Biological markers in osteoarthritis. Nat Clin Pract Rheumatol 3:346–356

    Article  PubMed  CAS  Google Scholar 

  8. Kojima K, Asmellash S, Klug CA, Grizzle WE, Mobley JA, Christein JD (2008) Applying proteomic-based biomarker tools for the accurate diagnosis of pancreatic cancer. J Gastrointest Surg 12(10):1683–1690

    Article  PubMed  Google Scholar 

  9. Jacot W, Lhermitte L, Dossat N, Pujol JL, Molinari N, Daurès JP (2008) Serum proteomic profiling of lung cancer in high-risk groups and determination of clinical outcomes. J Thorac Oncol 3(8):840–850

    Article  PubMed  Google Scholar 

  10. Ferino G, González-Díaz H, Delogu G, Podda G, Uriarte E (2008) Using spectral moments of spiral networks based on PSA/mass spectra outcomes to derive quantitative proteome-disease relationships (QPDRs) and predicting prostate cancer. Biochem Biophys Res Commun 372(2):320–325

    Article  PubMed  CAS  Google Scholar 

  11. Amadei GA, Cho CF, Lewis JD, Luyt LG (2010) A fast, reproducible and low-cost method for sequence deconvolution of 'on-bead' peptides via 'on-target' maldi-TOF/TOF mass spectrometry. J Mass Spectrom 45(3):241–251

    Article  PubMed  CAS  Google Scholar 

  12. Dong M, Wu M, Wang F, Qin H, Han G, Dong J (2010) Coupling strong anion-exchange monolithic capillary with MALDI-TOF MS for sensitive detection of phosphopeptides in protein digest. Anal Chem 82(7):2907–2915

    Article  PubMed  CAS  Google Scholar 

  13. Seibold E, Maier T, Kostrzewa M, Zeman E, Splettstoesser W (2010) Identification of Francisella tularensis by whole-cell matrix-assisted laser desorption ionization-time of flight mass spectrometry: fast, reliable, robust, and cost-effective differentiation on species and subspecies levels. J Clin Microbiol 48(4):1061–1069

    Article  PubMed  CAS  Google Scholar 

  14. Kondo N, Nishimura S (2009) MALDI-TOF mass-spectrometry-based versatile method for the characterization of protein kinases. Chemistry 15(6):1413–1421

    Article  PubMed  CAS  Google Scholar 

  15. Braun J, Sieper J (2009) Classification criteria for rheumatoid arthritis and ankylosing spondylitis. Clin Exp Rheumatol 27:S68–S73

    PubMed  CAS  Google Scholar 

  16. MacGregor AJ (1995) Classification criteria for rheumatoid arthritis. Baillières Clin Rheumatol 9(2):287–304

    Article  PubMed  CAS  Google Scholar 

  17. Pfeiffer E (1975) A short portable mental status questionnaire for the assessment of organic brain deficit in elderly patients. J Am Geriatr Soc 23(10):433–441

    PubMed  CAS  Google Scholar 

  18. Ketterlinus R, Hsieh SY, Teng SH, Lee H, Pusch W (2005) Fishing for biomarkers: analyzing mass spectrometry data with the new ClinPro Tools software. Biotechniques Suppl:37–40

  19. Hartwig S, Kotzka J, Müller H, Müller-Wieland D, Eckel J, Lehr S (2009) Enhancing mass spectrometry based serum profiling by a combination of free flow electrophoresis and ClinProt. Arch Physiol Biochem 115(5):259–266

    Article  PubMed  CAS  Google Scholar 

  20. Gianazza E, Mainini V, Castoldi G, Chinello C, Zerbini G, Bianchi C et al (2010) Different expression of fibrinopeptide A and related fragments in serum of type 1 diabetic patients with nephropathy. J Proteomics 73(3):593–601

    Article  PubMed  CAS  Google Scholar 

  21. Chinello C, Gianazza E, Zoppis I, Mainini V, Galbusera C, Picozzi S et al (2010) Serum biomarkers of renal cell carcinoma assessed using a protein profiling approach based on ClinProt technique. Urology 75(4):842–847

    Article  PubMed  Google Scholar 

  22. Ziganshin RKh, Alekseev DG, Arapidi GP, Ivanov VT, Moshkovskiĭ SA, Govorun VM (2008) Serum proteome profiling for ovarian cancer diagnosis using ClinProt magnetic bead technique and MALDI-TOF-mass-spectrometry. Biomed Khim 54(4):408–419

    PubMed  CAS  Google Scholar 

  23. Timms JF, Cramer R, Camuzeaux S, Tiss A, Smith C, Burford B et al (2010) Peptides generated ex vivo from serum proteins by tumor-specific exopeptidases are not useful biomarkers in ovarian cancer. Clin Chem 56(2):262–271

    Article  PubMed  CAS  Google Scholar 

  24. Chow SN, Chen RJ, Chen CH, Chang TC, Chen LC, Lee WJ et al (2010) Analysis of protein profiles in human epithelial ovarian cancer tissues by proteomic technology. Eur J Gynaecol Oncol 31(1):55–62

    PubMed  CAS  Google Scholar 

  25. Gámez-Pozo A, Sánchez-Navarro I, Nistal M, Calvo E, Madero R, Díaz E et al (2009) MALDI profiling of human lung cancer subtypes. PLoS ONE 4(11):e7731

    Article  PubMed  Google Scholar 

  26. Tsunemi S, Nakanishi T, Fujita Y, Bouras G, Miyamoto Y, Miyamoto A et al (2010) Proteomics-based identification of a tumor-associated antigen and its corresponding autoantibody in gastric cancer. Oncol Rep 23(4):949–956

    PubMed  CAS  Google Scholar 

  27. Breton J, Gage MC, Hay AW, Keen JN, Wild CP, Donnellan C et al (2008) Proteomic screening of a cell line model of esophageal carcinogenesis identifies cathepsin D and aldo-keto reductase 1 C2 and 1B10 dysregulation in Barrett's esophagus and esophageal adenocarcinoma. J Proteome Res 7(5):1953–1962

    Article  PubMed  CAS  Google Scholar 

  28. Zivanović S, Petrović-Rackov L, Zivanović A (2009) Arthrosonography and biomarkers in the evaluation of destructive knee cartilage osteoarthrosis. Srp Arh Celok Lek 137(11–12):653–658

    Article  PubMed  Google Scholar 

  29. Richardot P, Charni-Ben Tabassi N, Toh L, Marotte H, Bay-Jensen AC, Miossec P et al (2009) Nitrated type III collagen as a biological marker of nitric oxide-mediated synovial tissue metabolism in osteoarthritis. Osteoarthritis Cartilage 17(10):1362–1367

    Article  PubMed  CAS  Google Scholar 

  30. Qazi AA, Folkesson J, Pettersen PC, Karsdal MA, Christiansen C, Dam EB (2007) Separation of healthy and early osteoarthritis by automatic quantification of cartilage homogeneity. Osteoarthritis Cartilage 15(10):1199–1206

    Article  PubMed  CAS  Google Scholar 

  31. Kraus VB, Kepler TB, Stabler T, Renner J, Jordan J (2010) First qualification study of serum biomarkers as indicators of total body burden of osteoarthritis. PLoS ONE 5(3):e9739

    Article  PubMed  Google Scholar 

  32. Uchida T, Fukawa A, Uchida M, Fujita K, Saito K (2002) Application of a novel protein biochip technology for detection and identification of rheumatoid arthritis biomarkers in synovial fluid. J Proteome Res 1(6):495–499

    Article  PubMed  CAS  Google Scholar 

  33. Kamphorst JJ, van der Heijden R, DeGroot J, Lafeber FP, Reijmers TH, van El B et al (2007) Profiling of endogenous peptides in human synovial fluid by NanoLC-MS: method validation and peptide identification. J Proteome Res 6(11):4388–4396

    Article  PubMed  CAS  Google Scholar 

  34. Xiang Y, Matsui T, Matsuo K, Shimada K, Tohma S, Nakamura H et al (2007) Comprehensive investigation of disease-specific short peptides in sera from patients with systemic sclerosis: complement C3f-des-arginine, detected predominantly in systemic sclerosis sera, enhances proliferation of vascular endothelial cells. Arthritis Rheum 56(6):2018–2030

    Article  PubMed  CAS  Google Scholar 

  35. Dai Y, Hu C, Wang L, Huang Y, Zhang L, Xiao X et al (2010) Serum peptidome patterns of human systemic lupus erythematosus based on magnetic bead separation and MALDI-TOF mass spectrometry analysis. Scand J Rheumatol 39(3):240–246

    Article  PubMed  CAS  Google Scholar 

  36. Ruiz-Romero C, Carreira V, Rego I, Remeseiro S, López-Armada MJ, Blanco FJ (2008) Proteomic analysis of human osteoarthritic chondrocytes reveals protein changes in stress and glycolysis. Proteomics 8(3):495–507

    Article  PubMed  CAS  Google Scholar 

  37. Ruiz-Romero C, Calamia V, Mateos J, Carreira V, Martínez-Gomariz M, Fernández M et al (2009) Mitochondrial dysregulation of osteoarthritic human articular chondrocytes analyzed by proteomics: a decrease in mitochondrial superoxide dismutase points to a redox imbalance. Mol Cell Proteomics 8(1):172–189

    Article  PubMed  CAS  Google Scholar 

  38. Bo GP, Zhou LN, He WF, Luo GX, Jia XF, Gan CJ et al (2009) Analyses of differential proteome of human synovial fibroblasts obtained from arthritis. Clin Rheumatol 28(2):191–199

    Article  PubMed  Google Scholar 

  39. Chang X, Cui Y, Zong M, Zhao Y, Yan X, Chen Y et al (2009) Identification of proteins with increased expression in rheumatoid arthritis synovial tissues. J Rheumatol 36(5):872–880

    Article  PubMed  CAS  Google Scholar 

  40. de Seny D, Fillet M, Meuwis MA, Geurts P, Lutteri L, Ribbens C et al (2005) Discovery of new rheumatoid arthritis biomarkers using the surface-enhanced laser desorption/ionization time-of-flight mass spectrometry ProteinChip approach. Arthritis Rheum 52(12):3801–3812

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We thank the patients for donating the samples to the study, and the hospital staff who made this study possible. We thank Dr. Dai in the Clinical Medical Research Centre and the other members of his laboratory team for the processing of patient samples. In addition, we thank all of the study group members: Liling Huang, Yong Dai, Jiakai Chen, Xiaofen Chen (Department of Orthopedics and Traumatology, The Second Clinical Medical College of Jinan University, Shenzhen, Guangdong Province, China).

Author contributions

All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Dr. Dai had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study conception and design: Xiaohua Pan and Yong Dai. Acquisition of data: Xiaohua Pan, Jiakai Chen, and Xiaofen Chen. Analysis and interpretation of data: Xiaohua Pan and Liling Huang.

Competing interests

The authors have declared that no competing interests exist.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yong Dai.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pan, X., Huang, L., Chen, J. et al. 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. International Orthopaedics (SICOT) 36, 57–64 (2012). https://doi.org/10.1007/s00264-011-1258-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00264-011-1258-y

Keywords

Navigation