Title: The groove model of tibia-femoral osteoarthritis in the rat
Abstract: Purpose: Multiple experimental surgical models in small animals like the rat are currently used to study osteoarthritis (OA) and its potential treatment. However, these models have an important limitation as they often induce a permanent trigger during the course of OA, namely instability, counteracting the potential beneficial effects of therapy. Therefore, animal models of intrinsic cartilage damage, without a permanent trigger, have been described to induce joint degeneration and possibly being more sensitive to therapy. An example of such a model is the canine groove model of joint degeneration with features as observed in early OA. In this canine model, damage to the articular cartilage of the weight-bearing areas of the femoral condyles in the knee is the trigger for development of joint changes consistent with early OA. However, longitudinally in-vivo monitoring the disease progression is difficult in canine experiments. Besides, canine experiments can be limited performed due to restricted facilities and costs involved. The groove model can also be applied in the rat, where intrinsic cartilage damage is induced on the femoral trochlea. Here we report a modified groove model of the rat, where intrinsic cartilage damage on the weight bearing surface of the femoral condyles of a rat knee joint was induced, similar to the canine model. The subsequent degenerative joint changes were evaluated. Methods: In Ten male Wistar rats (Charles-River, Sulzfeld, Germany), 16 weeks of age, surgery was performed in one knee joint. During surgery the articular cartilage, of both the trochlear groove and the weight bearing areas of the femoral condyles, is damaged (grooved) without damaging the underlying subchondral bone. The contralateral knee joint served as an internal control. For a period of 12 weeks the subchondral bone parameters (Subchondral plate, trabecular bone and volume fraction) as well as the articular cartilage of the patella are longitudinally monitored by (contrast enhanced-)micro-CT (μCT) (Quatum FX, PerkinElmar, USA). Subsequently, OA severity is assessed, 6 and 12 weeks post-surgery, by the rat OARSI histopathology score by two observers blinded for study group. Directly induced damage by groove surgery was neglected for OA severity assessment. To analyze differences between the surgical induced and contralateral control knee joints the paired-samples T test was used. The study was approved by the Utrecht University Medical Ethical Committee for animal studies. Results: Inducing local cartilage damage on the femoral condyles and trochlea by groove surgery in rat knee joints resulted in mild, but statistically significant higher, joint degeneration at 6 weeks (5.2±0.8 vs 0.6±0.5; p<0.0001) and 12 weeks (4.8±0.7 vs 1±0.9; p <0.001) post-surgery compared to the contralateral control knee joint. Although the tibia plateau was not surgically damaged, increased articular cartilage degeneration compared to the tibia plateau of the control knee joints was observed (4.8±1 vs 1±0.9; p<0.01; see Fig. 1). No difference was found in synovial membrane inflammation between surgically damaged and control knee joints (0.7±0.5 vs 0.5±0.7; p>0.05). With contrast enhanced μCT scans clear loss of cartilage thickness could be observed of the patella cartilage 12 weeks post-surgery (121±48 vs 174±57 μm; p<0.05). In parallel, the amount of grey value was enhanced over time, indicating increased uptake of contrast agent in the articular cartilage, and thus more cartilage degeneration (2255±76 vs 1998±80; p<0.05). In addition, μCT imaging detected significant subchondral bone changes on the tibia compartment of the knee joints already 6 weeks after surgery compared to the control knee joints regarding mean subchondral plate thickness (264±19 vs 250±13 μm; p<0.05), mean trabecular bone thickness (199±14 vs 184±9 μm; p<0.001) and volume fraction (0.55±0.04 vs 0.51±0.04; p<0.01). Conclusions: Here we present results of the modified groove model of local cartilage damage in the rat, which leads to early degenerative joint changes with slow onset, in both the directly damaged (femur) as the opposite (untouched tibia) joint compartment. Besides, this model did not lead to local inflammation and permanent destabilization.