DEVELOPMENT OF OSTEOARTHRITIS IN THE KNEE JOINTS OF WISTAR RATS AFTERSTRENUOUS RUNNING EXERCISE IN A RUNNING WHEEL BY INTRACRANIAL SELF-STIMULATION

The influence of excessive running load on the development of knee ost eoarthritis (OA) was investigated in male Wistar rats. Running exercis es were performed in a running wheel using intracranial self-stimulati on to motivate Wistar rats to run daily distances of 500 m at 5 days/w eek. Hereby, ten rats ran a distance of 15 km within three weeks while a further ten rats run a total of 30 km within six weeks. Thirteen Wi star rats without running exercises served as controls. Complete knee joint sections of all rats were evaluated histologically using MANKINs grading system with categorization of the findings into non, mild mod erate, and severe osteoarthritis. In addition, immunoreactivity of the chondrocytes to MMP-3 as an important cartilage degrading enzyme in O A was assessed by immunostaining with monoclonal MMP-3 IgG antibodies. Histological assessment of the knee joint sections revealed a signifi cant increase in osteoarthritic changes with higher running load. Whil e in rats with 15 km running all but two knee joints showed mild OA, m oderate OA was the predominant finding in rats with 30 km running. In contrast, no OA was found in the controls. Immunostaining for MMP-3 re vealed a significant increase in immunoreactivity of the chondrocytes to MMP-3 with higher running load, indicating a running load-depending production of this cartilage-degrading enzyme in the course of increa sing OA. Compared to 47.4% immunoreactive chondrocytes to MMP-3 in the controls, this ratio rose to 70.4% in rats with 15 km running and eve n up to 89.9% in rats with 30 km running. In conclusion, in Wistar rat s, excessive running load leads to marked, running distance-depending osteoarthritic changes which are caused, at least in part, by an incre ase in MMP-3 production rising with greater running distance. Within t his exercise model of OA, intracranial self-stimulation is an effectiv e method to motivate Wistar rats to extremely excessive running in a r unning wheel. This model offers a wide range of further approaches to studying different processes of the development of OA.