Comparison between Subchondral Bone Change and Cartilage Degeneration in Collagenase- and DMM- induced Osteoarthritis (OA) Models in Mice

Osteoarthritis (OA) is a multifactorial disease affecting both the cartilage and the subchondral bone. However, animal models of OA cannot represent both of the changes and show variations depending on induction methods and animal species/strains. This study first investigated subchondral bone changes and its correlation with cartilage degeneration in two different OA models in C57Bl/6 mice. Experimental OA was produced by type II collagenase-induced osteoarthritis (CIOA) and destabilization of the medial meniscus (DMM). The subchondral plate and trabecular bone of the tibia were analyzed by micro-computed tomography and cartilage degeneration was analyzed histologically after safranin-O staining at 2, 4, 6 and 8 weeks. In the DMM model, cartilage degeneration was induced reproducibly and progressively with time. Progressive increase in subchondral bone volume, but not in bone thickness, was also observed in both subchondral bone plate and subchondral trabecular bone in the medial tibial area. The changes in subchondral bone volume correlated well with the histological cartilage degeneration (R-2=0.7870). In contrast, in the CIOA model, cartilage degeneration was relatively unstable, increasing only until 4 weeks and decreasing thereafter. No significant changes in subchondral bone were observed in all areas at all time points. These results suggest that the DMM OA mouse model is more reliable and useful than the CIOA model by virtue of its better representation of cartilage degeneration and subchondral bone change with high correlation coefficient.