A novel dual injury osteoarthritis (OA) model that combines destabilisation of the medial meniscus and cartilage damage leads to accelerated osteophytogenesis

IntroductionOsteoarthritis is associated with articular cartilage damage. While it is not known how disease pathogenesis is initiated, it is assumed that it can be via an isolated injury, or a combination of joint damage over time. Given the fact cartilage has poor regenerative capability, OA represents a major clinical challenge. Several murine models are used to study OA (e.g. destabilisation of the medial meniscus (DMM)), however do not combine simultaneous cartilage injury with joint destabilisation. The principle aim of this study was to investigate if combining cartilage damage and DMM accelerates the onset of OA-like symptoms.
MethodsOA was induced in mice via (a) transection of the medial meniscotibial ligament (DMM), (b) microblade scratches of articular cartilage (cartilage damage) or (c) combined DMM and cartilage scratch (DCS). Fourteen days post-surgery, dynamic weight bearing was assessed as an indirect measurement of pain, and microcomputered tomography (μCT) was used to monitor bone changes.
ResultsOsteophytes were present in all groups post-surgery. However, between groups there were observable differences in number, appearance, and bone volume (Fig. 1). Osteophytes in the DCS model encompassed a larger area of subchondral bone compared with DMM or cartilage scratch models (14.12 ±0.31 versus 12.4 ±0.62, 12.68 ±0.54, p<0.01 respectively). In DMM 6/8 mice developed protruding osteophytes with an arboreal-like structure. Osteophytes were present in all mice that underwent cartilage scratch surgery, and had a larger more calcified appearance. In the DCS model, all mice exhibited ≥2 large, protruding, calcified osteophytes. Finally, mice in the DCS model demonstrated a significant increase in front paw load compared with the other models, suggesting an increase in OA-like pain. 
ConclusionCombining DMM with cartilage damage provides a robust and reproducible model for OA-associated osteophytogenesis. This model also incorporates OA-related pain, arguably one of the most problematic and physically limiting symptoms of OA.