Effect of moderate increasing exercise on the mechanical balance of the knee joint in young rats

Purpose: It is hypothesized that the amount, duration and magnitude of mechanical loading are important factors that maintain the cartilage tissue in physiological condition. The underlying subchondral bone attached to the cartilage tissue and the cartilage-bone interface are influenced by the mechanical loading as well. In this study, we aimed to investigate adaptation of the rat knee joint to the mechanical demands. For this purpose, we applied load in the form of exercise using a moderate-intensity increasing running protocol. A series of analyses was performed to elucidate the response of cartilage and bone to this physical activity. Methods: Male Wistar rats (Charles River, Germany) with an age of 8 weeks were placed in 2 groups: a moderate running group that runs for 8 weeks with a slowly increasing running velocity - from 10 m/min for 10 min, up to 20 m/min for 1 hour (n = 10), and a control group without running (n = 10). Running takes place on a 5 lane motorized rodent treadmill (LE-8700; Panlab Harvard Apparatus). At starting point and after 8 weeks cartilage qPCR, micro-CT, histology and plasma FIB 3-2 (Artialis) was performed. Results: A total 24 km running within 8 weeks of this running protocol illustrates chondrocyte sensitivity and cartilage response to the mechanical loading (Fig. 1). At the end of the experiment, aggrecan was 1.55-fold up-regulated while MMP-2 was 2.38-fold down-regulated (P < 0.05) (Fig. 1A). The histological appearance of the chondrocytes also showed load-dependency, with more hypercellularity and hypertrophy in the running group (Fig. 1B). FIB3-2 as a plasma biomarker, interacts with the tissue inhibitor of metalloproteinase 3 (TIMP-3) and the elevated amount of FIB3-2 is expected in osteoarthritis samples. FIB3-2 is also known to be cleaved by several MMPs family including MMP-2. FIB3-2 levels dropped in the running group (from 52.7 ± 13.2 nM to 30.2 ± 8.4 nM) as compared to the control group (45.3 ± 15.0 nM to 33.3 ± 9.7 nM) (Fig. 1C). MicroCT analysis revealed an enhancement in bone response as a result of early moderate physical training where epiphysis bone parameters in the running group including thickness and bone volume fraction of subchondral bone tibia plateau as well as trabecular bone mass significantly increased compared with control animals (Fig. 2). Conclusions: Gradual increase of running up to a moderate level to 1120 m/h for one hour enhances aggrecan expression, reduces catabolic enzymatic activity of MMP-2 as well as increases subchondral bone thickness in the epiphysis area and leads to hypercellularity and hypertrophy of the chondrocytes. Conclusively, a moderate exercise program can significantly influence both bone remodeling and cartilage tissue adaptation