title: Nitrated type III collagen as a biological marker of nitric oxide-mediated synovial tissue metabolism in osteoarthritis.
abstract: OBJECTIVE
  Nitric oxide (NO) is a major mediator of joint tissue inflammation and damage in osteoarthritis (OA) and mediates the nitration of tyrosine (Y*) residues in proteins. We investigated the nitration of type III collagen, a major constituent of synovial membrane, in knee OA.
  
  
  METHODS
  A polyclonal antibody directed against the nitrated QY*DSY*DVKSG sequence from type III collagen N-telopeptide was generated. Synovial tissues from patients with knee OA (n=4) and rheumatoid arthritis (RA, n=4) were analyzed by immunohistochemistry for IIINys. Serum IIINys levels were measured by enzyme-linked immunosorbent assay in 87 patients with painful knee OA (mean age: 63.0+/-8.0 years, Kellgren-Lawrence score II-III) and in 40 sex and age-matched healthy controls.
  
  
  RESULTS
  Competition experiments using various nitrated and un-nitrated type III collagen and derived sequences, showed that the antibody was highly specific for the nitrated IIINys sequence. High IIINys immunoreactivity was detected in the synovial tissues from all patients with OA and RA with a preferential localization in the intimal layer. Serum IIINys levels were on average 1.5-fold higher (P<0.0001) in patients with knee OA than in healthy controls and significantly correlated with C-reactive protein values (r=0.40, P<0.005).
  
  
  CONCLUSIONS
  Nitration of tyrosine residues of type III collagen N-telopeptide is increased in the synovial tissue of patients with knee OA. Measurements of serum IIINys level may be useful for the clinical investigation of oxidative-related alterations of synovial tissue metabolism in OA.
authors.affiliation: CCBR-SYNARC, Lyon, France.
authors.forename: P
authors.initials: P
authors.lastname: Richardot
authors.forename: N
authors.initials: N
authors.lastname: Charni-Ben Tabassi
authors.forename: L
authors.initials: L
authors.lastname: Toh
authors.forename: H
authors.initials: H
authors.lastname: Marotte
authors.forename: A-C
authors.initials: AC
authors.lastname: Bay-Jensen
authors.forename: P
authors.initials: P
authors.lastname: Miossec
authors.forename: P
authors.initials: P
authors.lastname: Garnero
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D024042:Collagen Type I; D024061:Collagen Type III / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000378:metabolism*; D020370:Osteoarthritis, Knee / Q000097:blood / Q000378:metabolism*; D010455:Peptides / Q000097:blood; D013583:Synovial Membrane / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D024061:Collagen Type III; D009566:Nitrates; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D014443:Tyrosine