The utility of measuring C-terminal telopeptides of Collagen type II (CTX-II) in serum and synovial fluid samples for estimation of articular cartilage status in experimental models of destructive joint diseases

Objective: To characterize and validate a novel enzyme-linked immunoassay for measuring cross-linked dimer forms of C-terminal telopeptides of type II collagen (CTX-II) in serum and synovial fluid of rodents, and investigate whether CTX-II measurements can reflect joint status in two established animal models of destructive joint diseases. Methods: Firstly, the specificity, in vivo validity, antigen recovery, and reproducibility of the assay were investigated. Secondly, we induced arthritis in rats using either bovine collagen type II or mono-iodoacetate. CTX-II levels were measured in the serum and synovial fluid of the affected femoro-tibial joint and correlated with microscopic severity of joint lesions as determined by validated scoring systems. Results: The F4601 monoclonal antibody (mAb) is highly specific for the EKGPDP sequence at the CTX-II. Strong CTX-II signals were detected during enzymatic degradation of articular cartilage explants by matrix metalloproteinase (MMP)-9 or MMP-13. The assay presented a good degree of precision and reproducibility (inter- and intra-assay coefficient of variations< 8.0%). In the collagen-induced arthritis (CIA) model, the assay indicated markedly increased levels of CTX-II in both the synovial fluid and the serum. Furthermore, CTX-II levels in both the synovial fluid (r= 0.76; P< 0.0001) and the serum (r= 0.85; P< 0.0001) showed strong correlations with the microscopic severity scores of joint lesions at Day 22. In the mono-iodoacetate-induced arthritis (MIA) model, CTX-II concentration in the synovial fluid (r= 0.53; P < 0.0001), but not in the serum, correlated with the microscopic severity score. Conclusions: The Preclinical CTX-II assay could provide a useful supplement to currently available methods for the non-invasive assessment of cartilage status. The utility of serum CTX-II to reflect joint status appeared to be limited to systemic forms of destructive joint diseases. (C) 2006 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.