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Urinary Collagen Type II C-Telopeptide Fragments Are Sensitive Markers of Matrix Metalloproteinase-Dependent Cartilage Degradation in Rat Adjuvant-Induced Arthritis
FREDERIC DE CEUNINCK, MASSIMO SABATINI, VERONIQUE RENOUX, GUILLAUME de NANTEUIL, and PHILIPPE PASTOUREAU
ABSTRACT. 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. (J Rheumatol 2003;30:1561-4) Key Indexing Terms:
ADJUVANT-INDUCED ARTHRITIS From the Departments of Rheumatology and Chemistry, Institut de Recherches Servier, Suresnes, France. F. De Ceuninck, PhD, Scientist; M. Sabatini, PhD, Project Leader; V. Renoux, Technician; G. de Nanteuil, PhD, Director, Division of Chemistry; P. Pastoureau, PhD, Project Leader. Address reprint requests to Dr. F. De Ceuninck, Division of Rheumatology, Institut de Recherches Servier, 11 rue des Moulineaux, 92150 Suresnes, France. E-mail: frederic.deceuninck@fr.netgrs.com Submitted July 23, 2002; revision accepted February 2, 2003. |