Urinary collagen type II C-telopeptide fragments are sensitive markers of matrix metalloproteinase-dependent cartilage degradation in rat adjuvant-induced arthritis

• Published in: Journal of rheumatology 2003-07, Vol.30 (7), p.1561-1564
• Main Authors: DE CEUNINCK, Frederic, SABATINI, Massimo, RENOUX, Veronique, DE NANTEUIL, Guillaume, PASTOUREAU, Philippe
• Format: Article
• Language: English
• Subjects: Animals; Arthritis, Experimental - enzymology; Arthritis, Experimental - physiopathology; Arthritis, Experimental - urine; Biological and medical sciences; Cartilage, Articular - drug effects; Cartilage, Articular - enzymology; Collagen - urine; Collagen Type I; Collagen Type II - urine; Diseases of the osteoarticular system; Enzyme Inhibitors - pharmacology; Female; Freund's Adjuvant; Inflammatory joint diseases; Inhibitory Concentration 50; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases - metabolism; Medical sciences; Peptide Fragments - urine; Peptides - urine; Rabbits; Rats; Rats, Inbred Lew
• ISSN: 0315-162X; 1499-2752

OBJECTIVE: To assess the relevance of collagen type II C-telopeptide fragments (CTX-II) as markers of cartilage degradation during adjuvant-induced arthritis in rats. METHODS: Rats were injected with Freund's adjuvant on day 0 and treated orally for 21 days twice a day with vehicle or 10 or 20 mg/kg of a newly designed matrix metalloproteinase inhibitor (MMP-Inh). Urine samples were collected for 24 h between days 19 and 20 and the concentration of the cartilage-derived CTX-II was measured with a 2-site, sandwich-type ELISA. To assess arthritis, inflammatory scores were determined, and changes in paw volumes were measured by plethysmography. RESULTS: On day 21, the inflammation was generalized in rats injected with Freund's adjuvant. The urinary concentration of CTX-II was significantly higher in arthritic rats than in control non-injected rats. Oral treatment of arthritic rats with MMP-Inh dramatically decreased the concentration of CTX-II in urine, with values returning to those of controls. Treatment simultaneously reduced the clinical variables of the disease. CONCLUSION: These results demonstrate that fragments of type II collagen in urine can be used as a measure of cartilage degradation in arthritic rats as well as potent non-invasive markers of the efficacy of chondroprotective treatments.