Significance of the serum CTX-II level in an osteoarthritis animal model: a 5-month longitudinal study.
OBJECTIVE
The aim of this study was to investigate the clinical value of serum measurement of C-telopeptide of type II collagen (CTX-II). In correlation with late stages of osteoarthritis (OA) evaluated with histological assessment, the evolution of serum CTX-II concentration was followed during a 20-week longitudinal study in rabbit anterior cruciate ligament transection (ACLT) OA model in adult and growing animals.


METHODS
OA was induced in five adult and nine growing rabbits. Four adult and four young rabbits were unoperated. Serum sampling was made at week 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16 and 20 after the surgery in all rabbits. Animals were euthanized 20 weeks after the surgery. Serum CTX-II levels were analyzed with a recently available enzyme-linked immunosorbent assay (ELISA) kit, the protocol of which has been modified to increase the sensitivity of the test.


RESULTS
Significant differences for the CTX-II levels at W3, W6, W8, W10, W12, W14, W16 and W20 were observed between the adult ACLT and the control groups. A negative correlation between CTX-II levels and cartilage thickness of the medial compartment of the knee at W8, W10, W12 and a positive correlation between the CTX-II levels and the histomorphological score of the medial compartment of the knee at W3, W6, W8, W10, W12 were noted in adult animals. In young animals, operated or not, we observed high CTX-II levels at the beginning of the study, which decreased until the end.


CONCLUSIONS
Our results suggest the interest of the serum CTX-II monitoring for the OA progression and the relevance of the multiple time point analysis of this biomarker. Moreover, they address the question of the importance of correctly choosing the age of the animals used in the pre-clinical studies of OA.
Université de Lyon, ISPB-Faculté de Pharmacie, École Nationale Vétérinaire de Lyon, UPSP 2007-03-135 RTI2B, France. duclosmed@hotmail.com
M E
ME
Duclos
O
O
Roualdes
R
R
Cararo
J C
JC
Rousseau
T
T
Roger
D J
DJ
Hartmann
D000818:Animals; D000070598:Anterior Cruciate Ligament Injuries; D015415:Biomarkers / Q000097:blood; D002358:Cartilage, Articular / Q000473:pathology; D024043:Collagen Type II / Q000097:blood*; D004195:Disease Models, Animal; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D008137:Longitudinal Studies; D020370:Osteoarthritis, Knee / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000097:blood*; D011817:Rabbits
D015415:Biomarkers; D024043:Collagen Type II; D010446:Peptide Fragments; C543437:collagen II C-telopeptide