Establishment of a rat model of chronic osteoarthritis by intra-articular injection combined with treadmill exercise

doi:10.3969/j.issn.2095-4344.0821

Abstract

Abstract:

BACKGROUND: Establishment of an animal model of osteoarthritis is an important means to study the pathogenesis, prevention and treatment of osteoarthritis.
OBJECTIVE: To further verify the feasibility of establishing a rat model of osteoarthritis by intra-articular injection combined with treadmill exercise.
METHODS: The rats were randomly divided into sedentary, low-intensity (incline 0° and speed 15 m/min), moderate-intensity (incline 5° and speed 20 m/min) and high-intensity (incline 10° and speed 27 m/min) groups (n=6 per group). The acute injury of the knee joint was induced by injecting kaolin and carrageen-λ into the articular cavity. At 3 days after modeling, the adaptive exercise was conducted at a low speed, and 5 days later the formal training was conducted, 1 hour per day and 1 day off every week for continuous 6 weeks. The degree of joint swelling was measured once a week. The rats were sacrificed after 6 weeks of exercise and the paraffin continuous sections of knee joints were prepared and stained with hematoxylin and eosin, and safranin 0 and fast green to observe the pathological changes of articular cartilage. The contents of matrix metalloproteinase-3, tissue inhibitor of metalloproteinases 1, and interleukin-1β in synovial tissues were detected with ELISA kits. The content of superoxide dismutase in serum was measured by xanthine oxidase method, and the expression of collagen type II was detected by immunohistochemistry.
RESULTS AND CONCLUSION: Compared with the sedentary group, the histopathological scores were significantly increased in the moderate-, and high-intensity groups (P < 0.05 or P < 0.01); the degree of joint swelling was significantly increased (P < 0.05 or P < 0.01); the contents of matrix metalloproteinase-3, tissue inhibitor of metalloproteinases 1, and interleukin-1β in synovial tissues were significantly up-regulated (P < 0.01), and the tissue inhibitor of metalloproteinases 1/matrix metalloproteinase-3 ratio was significantly reduced (P < 0.01); the level of superoxide dismutase in serum and the average optical density value of collagen type II in the articular cartilage were significantly decreased (P < 0.01). The average optical density value of collagen type II in the low-intensity group was significantly reduced (P < 0.05), but there was no significant change in the other indexes. The changes in the indexes in the moderate- and high-intensity groups were significantly different from those in the low-intensity group (P < 0.01 or P < 0.05). In the high-intensity group, the content of matrix metalloproteinase-3 in serum was significantly higher (P < 0.01) and the tissue inhibitor of metalloproteinases 1/matrix metalloproteinase-3 ratio in the synovium was significantly lower (P < 0.05) compared with the moderate-intensity group, but there was no significant difference in the other indexes between the two groups. These results indicate that the moderate- and high-intensity exercise can aggravate joint swelling and histopathological abnormalities, aggravate oxidative and inflammatory damage and accelerate cartilage degradation in rats, eventually resulting in chronic osteoarthritis. According to the actual operation, the moderate-intensity exercise is the best choice for establishing the chronic osteoarthritis model in rats.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Key words: Osteoarthritis, Cytokines, Proteoglycans, Collagen Type II, Tissue Engineering

CLC Number:

R318

Chen Shi-jie1, 2, Zhu Yang-xiong1, 2, Lao Wen-yan1, 2, 3, Zhou Yan-li1, 2, Zhao Xiao-hong1, 2, 3. Establishment of a rat model of chronic osteoarthritis by intra-articular injection combined with treadmill exercise[J]. Chinese Journal of Tissue Engineering Research, 2018, 22(24): 3849-3856.

Figures/Tables 3

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