Pap G, Eberhardt R, Stürmer I, Machner A, Schwarzberg H, Roessner A, Neumann W
Department of Orthopedic Surgery, University of Magdeburg School of Medicine, Germany.
Pathol Res Pract. 1998;194(1):41-7. doi: 10.1016/S0344-0338(98)80010-1.
The influence of excessive running load on the development of knee osteoarthritis (OA) was investigated in male Wistar rats. Running exercises were performed in a running wheel using intracranial self-stimulation to motivate Wistar rats to run daily distances of 500 m at 5 days/week. 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 Wistar 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 moderate, and severe osteoarthritis. In addition, immunoreactivity of the chondrocytes to MMP-3 as an important cartilage degrading enzyme in OA was assessed by immunostaining with monoclonal MMP-3 IgG antibodies. Histological assessment of the knee joint sections revealed a significant increase in osteoarthritic changes with higher running load. While in rats with 15 km running all but two knee joints showed mild OA, moderate OA was the predominant finding in rats with 30 km running. In contrast, no OA was found in the controls. Immunostaining for MMP-3 revealed 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 increasing 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 even up to 89.9% in rats with 30 km running. In conclusion, in Wistar rats, excessive running load leads to marked, running distance-depending osteoarthritic changes which are caused, at least in part, by an increase in MMP-3 production rising with greater running distance. Within this exercise model of OA, intracranial self-stimulation is an effective method to motivate Wistar rats to extremely excessive running in a running wheel. This model offers a wide range of further approaches to studying different processes of the development of OA.
在雄性Wistar大鼠中研究了过度跑步负荷对膝关节骨关节炎（OA）发展的影响。利用颅内自我刺激在跑步轮中进行跑步锻炼，以促使Wistar大鼠每周5天每天跑500米的距离。据此，10只大鼠在三周内跑了15公里，而另外10只大鼠在六周内总共跑了30公里。13只未进行跑步锻炼的Wistar大鼠作为对照。使用MANKINs分级系统对所有大鼠的完整膝关节切片进行组织学评估，并将结果分类为无、轻度、中度和重度骨关节炎。此外，通过用单克隆MMP - 3 IgG抗体进行免疫染色，评估软骨细胞对OA中一种重要的软骨降解酶MMP - 3的免疫反应性。膝关节切片的组织学评估显示，随着跑步负荷增加，骨关节炎变化显著增加。在跑了15公里的大鼠中，除两只膝关节外，其余所有膝关节均显示轻度OA，而在跑了30公里的大鼠中，中度OA是主要发现。相比之下，对照组未发现OA。MMP - 3免疫染色显示，随着跑步负荷增加，软骨细胞对MMP - 3的免疫反应性显著增加，表明在OA进展过程中，这种软骨降解酶的产生与跑步负荷有关。与对照组中47.4%对MMP - 3有免疫反应性的软骨细胞相比，在跑了15公里的大鼠中这一比例升至70.4%，在跑了30公里的大鼠中甚至高达89.9%。总之，在Wistar大鼠中，过度跑步负荷会导致明显的、与跑步距离相关的骨关节炎变化，这至少部分是由随着跑步距离增加而上升的MMP - 3产生增加所引起的。在这个OA运动模型中，颅内自我刺激是促使Wistar大鼠在跑步轮中进行极度过度跑步的有效方法。该模型为研究OA发展的不同过程提供了广泛的进一步研究途径。
