title: Discovery and biochemical characterisation of four novel biomarkers for osteoarthritis.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: GIGA Research, Laboratory of Rheumatology, University of Liège, CHU Liège, Belgium. ddeseny@chu.ulg.ac.be
authors.forename: Dominique
authors.initials: D
authors.lastname: de Seny
authors.forename: Mohammed
authors.initials: M
authors.lastname: Sharif
authors.forename: Marianne
authors.initials: M
authors.lastname: Fillet
authors.forename: Gaël
authors.initials: G
authors.lastname: Cobraiville
authors.forename: Marie-Alice
authors.initials: MA
authors.lastname: Meuwis
authors.forename: Raphaël
authors.initials: R
authors.lastname: Marée
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Hauzeur
authors.forename: Louis
authors.initials: L
authors.lastname: Wehenkel
authors.forename: Edouard
authors.initials: E
authors.lastname: Louis
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Merville
authors.forename: John
authors.initials: J
authors.lastname: Kirwan
authors.forename: Clio
authors.initials: C
authors.lastname: Ribbens
authors.forename: Michel
authors.initials: M
authors.lastname: Malaise
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D001798:Blood Proteins / Q000032:analysis*; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000097:blood* / Q000175:diagnosis / Q000378:metabolism; D010446:Peptide Fragments / Q000032:analysis / Q000097:blood; D040901:Proteomics / Q000379:methods; D015203:Reproducibility of Results; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D013582:Synovial Fluid / Q000737:chemistry
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D010446:Peptide Fragments