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Discovery and biochemical characterisation of four novel biomarkers for osteoarthritis
  1. Dominique de Seny1,
  2. Mohammed Sharif2,
  3. Marianne Fillet3,
  4. Gaël Cobraiville1,
  5. Marie-Alice Meuwis4,
  6. Raphaël Marée4,
  7. Jean-Philippe Hauzeur1,
  8. Louis Wehenkel5,
  9. Edouard Louis6,
  10. Marie-Paule Merville3,
  11. John Kirwan7,
  12. Clio Ribbens1,
  13. Michel Malaise1
  1. 1GIGA Research, Laboratory of Rheumatology, University of Liège, CHU Liège, Belgium
  2. 2Department of Anatomy, University of Bristol, Bristol, UK
  3. 3GIGA Research, Laboratory of Clinical Chemistry, University of Liège, CHU Liège, Belgium
  4. 4GIGA Proteomics and Bioinformatics Platform, University of Liège, CHU Liège, Belgium
  5. 5GIGA Research, Bioinformatics and Modeling Unit, Department of Electrical Engineering & Computer Science, University of Liège, CHU Liège, Belgium
  6. 6Laboratory of Hepato-Gastroenterology, University of Liège, CHU Liège, Belgium
  7. 7Rheumatology Unit, University of Bristol, Bristol, UK
  1. Correspondence to Dominique de Seny, Department of Rheumatology, Tour GIGA +2, CHU, 4000 Liège, Belgium; ddeseny{at}chu.ulg.ac.be

Abstract

Objective Knee osteoarthritis (OA) is a heterogeneous, complex joint pathology of unknown aetiology. Biomarkers have been widely used to investigate OA but currently available biomarkers lack specificity and sensitivity. Therefore, novel biomarkers are needed to better understand the pathophysiological processes of OA initiation and progression.

Methods Surface enhanced laser desorption/ionisation-time of flight-mass spectrometry proteomic technique was used to analyse protein expression levels in 284 serum samples from patients with knee OA classified according to Kellgren and Lawrence (K&L) score (0–4). OA serum samples were also compared to serum samples provided by healthy individuals (negative control subjects; NC; n=36) and rheumatoid arthritis (RA) patients (n=25). Proteins that gave similar signal in all K&L groups of OA patients were ignored, whereas proteins with increased or decreased levels of expression were selected for further studies.

Results Two proteins were found to be expressed at higher levels in sera of OA patients at all four K&L scores compared to NC and RA, and were identified as V65 vitronectin fragment and C3fpeptide. Of the two remaining proteins, one showed increased expression (unknown protein at m/z of 3762) and the other (identified as connective tissue-activating peptide III protein) was decreased in K&L scores >2 subsets compared to NC, RA and K&L scores 0 or 1 subsets.

Conclusion The authors detected four unexpected biomarkers (V65 vitronectin fragment, C3f peptide, CTAP-III and m/z 3762 protein) that could be relevant in the pathophysiological process of OA as having significant correlation with parameters reflecting local inflammation and bone remodelling, as well as decrease in cartilage turnover.

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Footnotes

  • DdS and MS contributed equally to this work.

  • Funding This study was supported by the National Fund for Scientific Research (FNRS, Belgium) and the ‘Fond d'Investissement pour la Recherche Scientifique’ (FIRS), CHU Liège, Belgium. MF is Research Associate and M-PM and EL are Senior Research Associates at FNRS (National Fund for Scientific Research).

  • Patient consent Obtained.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the institutional review boards (Research Ethics Committee) of both the United Bristol Healthcare NHS trust, Bristol, UK, and the University Hospital, CHU Liège, Belgium.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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