AB0063 AGING CARTILAGE IN WILD-TYPE MICE: AN OBSERVATIONAL STUDY

Abstract

Background:Many animal models of osteoarthritis (OA) have been used to study the pathogenesis of cartilage degeneration1. In mice, spontaneous OA can occur in wild-type or genetically modified animals. The first report of spontaneous OA developing in wild-type mice was published in 19562and changes affecting the knee joint were further related to OA by using ultrastructural- histochemical analyses. However, a quantitative assessment of age-related evolution of OA-type cartilage lesions is lacking. The OA Research Society International (OARSI) grading score was adapted to semi-quantify histopathogical changes occurring in OA animal models, including mice3. The OARSI score has been used to describe changes occurring in induced or genetic OA mouse models but not to describe spontaneous age-related evolution of OA-type cartilage lesions in wild-type mice.Objectives:We aimedto describe the spontaneous evolution of age-related changes affecting knee joint articular cartilage, walking speed and a serum biomarker of cartilage remodeling in C57BL/6 wild-type male mice.Methods:Histological changes were assessed by the OARSI score in newborn, 1-week- and 1-, 3-, 6-, 9- and 12-month-old C57BL/6 wild-type male mice, walking speed by the Locotronic system, and serum C-terminal telopeptide of type II collagen (CTX-II) content by ELISA in 1-, 3-, 6-, and 9-month-old C57BL/6 wild-type male mice.Results:Mean (SD) OARSI score increased from 0.2(0.3) to 1.3(0.6) (p=0.03) between 1 and 3 months of age and from 1.3(0.6) to 3.3(0.6) (p=0.04) between 3 and 6 months of age. Mean walking speed was stable between 1 and 6 months of age but decreased from 11.4(1.8) to 3.2(0.8) cm.s-1 (p=0.03) between 6 and 9 months of age. Serum CTX-II content was maximal at 1 month of age, then decreased from 12.2(8.5) to 2.4(8.4) pg/ml (p=0.02) between 1 and 3 months of age, remaining low and stable thereafter.Conclusion:C57BL/6 wild-type male mice showed continuously increasing osteoarthritic changes but delayed decreasing walking speed with age. These variations were maximal between 3 and 9 months of age. Maximal serum CTX-II content preceded these changes.