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


CONCLUSIONS
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.
De Ceuninck
Frederic
F
Department of Rheumatology, Institut de Recherches Servier, Suresnes, France. frederic.deceuninck@fr.netgrs.com
Sabatini
Massimo
M
Renoux
Veronique
V
de Nanteuil
Guillaume
G
Pastoureau
Philippe
P
D000818:Animals; D001169:Arthritis, Experimental / Q000201:enzymology* / Q000503:physiopathology / Q000652:urine; D002358:Cartilage, Articular / Q000187:drug effects / Q000201:enzymology*; D003094:Collagen / Q000652:urine; D024042:Collagen Type I; D024043:Collagen Type II / Q000652:urine*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005620:Freund's Adjuvant; D020128:Inhibitory Concentration 50; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D010446:Peptide Fragments / Q000652:urine; D010455:Peptides / Q000652:urine; D011817:Rabbits; D051381:Rats; D011917:Rats, Inbred Lew
D024042:Collagen Type I; D024043:Collagen Type II; D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D010446:Peptide Fragments; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D003094:Collagen; D005620:Freund's Adjuvant; D020782:Matrix Metalloproteinases