The release of crosslinked peptides from type II collagen into human synovial fluid is increased soon after joint injury and in osteoarthritis

Arthritis Rheum. 2003 Nov;48(11):3130-9. doi: 10.1002/art.11326.


Objective: To determine concentrations of crosslinked C-telopeptide fragments of type II collagen (CTX-II) in synovial fluid (SF) from patients with joint injury, osteoarthritis (OA), or other knee arthritides.

Methods: Two study groups were used: a cross-sectional group, which included healthy-knee volunteers (reference group [REF]) and patients with pseudogout (PPA), an anterior cruciate ligament tear with or without a meniscus tear (INJ), or primary knee OA (POA); and a longitudinal group, which included patients with arthroscopic cartilage changes or septic arthritis. CTX-II was quantified by competition enzyme-linked immunosorbent assay (ELISA) based on a monoclonal antibody that recognized the C-terminus of the peptide EKGPDP as a proteolytic neoepitope. Aggrecan fragments, matrix metalloproteinases 1 and 3, and tissue inhibitor of metalloproteinases 1 were determined by ELISAs.

Results: Concentrations of CTX-II in SF were higher in patients with PPA, INJ, and POA than in the REF group (P < 0.001). After joint injury, mean levels of CTX-II in SF were increased above REF levels at all time intervals (P < 0.001), and were highest within hours after trauma. In those in the longitudinal study group with joint cartilage damage, variation coefficients for CTX-II were 81% (between patients) and 64% (within patient), monitored over 1 year. In a patient with septic arthritis, SF CTX-II increased at the onset of symptoms, and peaked 30-fold higher than the baseline. Concentrations of all biomarkers decreased with successful treatment.

Conclusion: This is the first report to describe the release into SF of soluble molecular fragments specific for the degradation of mature, crosslinked, type II collagen (CII) in human OA and joint injury. The results provide strong evidence that the integrity of the CII network of cartilage is compromised soon after joint injury and in arthritis. This early degradation of CII may represent an important treatment target.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anterior Cruciate Ligament / metabolism
  • Anterior Cruciate Ligament Injuries
  • Arthritis, Infectious / metabolism
  • Biomarkers / analysis
  • Chondrocalcinosis / metabolism
  • Collagen Type II / metabolism*
  • Cross-Sectional Studies
  • Female
  • Humans
  • Knee Injuries / metabolism*
  • Male
  • Middle Aged
  • Osteoarthritis, Knee / metabolism*
  • Peptide Fragments / metabolism*
  • Procollagen / metabolism*
  • Synovial Fluid / metabolism*
  • Tibial Meniscus Injuries


  • Biomarkers
  • Collagen Type II
  • Peptide Fragments
  • Procollagen
  • procollagen type II carboxy-terminal peptide