| Abstract | 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 CVs< 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. |
| Authors | S Oestergaard, L Chouinard, N Doyle, M A Karsdal, S Y Smith, P Qvist, L B Tankó
(Affiliation: Nordic Bioscience A/S, Herlev, Denmark. soe at nordicbioscience.com)
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| Journal | Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society
(Osteoarthritis Cartilage)
Vol. 14
Issue 7
Pg. 670-9
(Jul 2006)
ISSN: 1063-4584 England |
| PMID | 16500121
(Publication Type: Journal Article)
|
| Chemical References |
- Collagen Type I
- Collagen Type II
- Peptides
- collagen type I trimeric cross-linked peptide
|
| Topics |
- Animals
- Arthritis, Experimental
(blood, pathology)
- Cartilage, Articular
(pathology)
- Collagen Type I
(blood, chemistry)
- Collagen Type II
(blood, chemistry)
- Disease Models, Animal
- Enzyme-Linked Immunosorbent Assay
(methods, standards)
- Joints
(pathology)
- Peptides
(blood, chemistry)
- Rats
- Reproducibility of Results
- Synovial Fluid
(chemistry)
|
