Accelerated osteoarthritic-like symptoms in a novel dual injury model combining destabilisation of the medial meniscus and cartilage damage

Osteoarthritis(OA) is associated with articular cartilage damage. It is assumed OApathogenesis can be initiated via an isolated injury, or an accumulation of joint damage over time. OA represents a major clinical challenge due to the poor regenerative capability of cartilage. Several murine models are used to study OA (e.g. destabilisation of the medial meniscus (DMM)), however, they do not combine simultaneous joint destabilisation with cartilage damage. The principle aim of this study was to investigate if combining DMM and cartilage damage could accelerate the onset of OA-like symptoms.

OA was induced in C57BL/6 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). Seven and 14 days post-surgery, inflammation, cartilage degradation and bone changes were monitored using histology and microcomputered tomography. Dynamic weight bearing was assessed as an indirect measurement of pain at 14 days.

Osteophytes were observed in all groups at days 7 and 14 post-surgery. When compared with DMM and cartilage damage models, osteophytes were visually larger and more numerous in the DCS model. Osteophyte total bone volume (BV) was greater at day 14 in both cartilage damage and DCS models; these osteophytes also encompassed a larger surface area of subchondral bone (14.12±0.31 versus 12.4±0.62, 12.68±0.54,p<0.01 respectively). With regard to other bone changes, at day 7 there was no detectable increase in BV and osteosclerosis was absent, but by day 14 osteosclerosis was detectable in both DMM and DCS models. Assessment of cartilage at day 14, revealed that there was a significant increase in damage in the DCS model when compared with DMM and cartilage damage models(p<0.01). Furthermore, there was a significant increase in synovitis in the DCS model compared with the cartilage scratch model (p<0.05). In mice that underwent DCS surgery there was significant increase in front paw load compared with the other models. At day 14 a positive correlation was observed between osteophyte number and front paw load (r=0.69, p=0.003).

The combination of DMM and cartilage damage provides a robust and reproducible model for OA-associated joint changes, suggesting this novel dual injury model not only accelerates osteophytogenesis, but also includes features of OA-related pain; arguably one of the most problematic and physically limiting symptoms of OA.