Abstract
IntroductionThe effect of intra-articular injection of matrix metalloproteinase (MMP)-3 inhibitor was investigated in a rat model to understand the role of MMP-3 in cartilage degradation induced by excessive loading from running.MethodsA total of 24 male Wistar rats were randomly assigned into groups of sedentary control (SED), high-intensity running (HIR), HIR + low dosage of MMP-3 Inhibitor I (HIRI1), and HIR + high dosage of MMP-3 Inhibitor I (HIRI2). Rats in the HIR, HIRI1 and HIRI2 groups were intensively trained for six weeks on the treadmill. Those in HIRI1 and HIRI2 groups were provided bilateral intra-articular injections of 80 μL of 0.2 mM and 2 mM MMP-3 Inhibitor I in knee joints once a week, respectively. Blood samples were collected to measure serum MMP-3 level using ELISA. Femoral condyles were collected to observe cartilage characteristics by histochemistry, and MMP-3 as well as collagen II was measured by immunohistochemistry. In addition, cartilage samples were obtained to assess MMP-3 mRNA expression by RT-PCR.ResultsHistological examination showed osteoarthritic changes in rats after six weeks of high intensity running. In comparison to the SED group, significant decreases in glycosaminoglycans (GAG) and collagen content were found in the HIR group, which corresponded to significant increase in serum MMP-3 level, cartilage MMP-3 activity and gene expression. However, such a degradative process was considerably retarded by intra-articular injection of MMP-3 inhibitor at higher dosage. Statistical differences were found between the HIR and HIRI2 groups with regard to GAG and collagen II content, serum MMP-3 level, cartilage MMP-3 activity and gene expression.ConclusionsHigh-intensity running for six weeks may lead to cartilage degradation in a rat model. It was shown that the chrondroprotective effect was offered by the use of intra-articular injection of MMP-3 inhibitor. MMP-3 acts as the key mediator of this catabolic change under such mechanical condition. The results also showed that MMP-3 selective inhibitor may be an effective option for retarding such osteoarthritic changes.
Highlights
The effect of intra-articular injection of matrix metalloproteinase (MMP)-3 inhibitor was investigated in a rat model to understand the role of matrix metalloproteinases (MMPs)-3 in cartilage degradation induced by excessive loading from running
In this current study, a MMP-3 selective inhibitor was administrated to observe whether it offered a protective effect on cartilage degradation induced by excessive running loading and, subsequent to a further understanding of the roles, whether MMP-3 could have a part in the degradation of cartilage extracellular matrix (ECM) under such mechanical conditions
Experimental animals and study protocol A total of 24 male Wistar rats (12 to 13 weeks old, weighing 200 to 250 g) were randomly and evenly assigned to one of four groups as follows: 1) sedentary control (SED), 2) high intensity running (HIR), 3) high intensity running + low dosage of MMP-3 Inhibitor I (HIRI1), and 4) high intensity running + high dosage of MMP-3 Inhibitor I (HIRI2)
Summary
The effect of intra-articular injection of matrix metalloproteinase (MMP)-3 inhibitor was investigated in a rat model to understand the role of MMP-3 in cartilage degradation induced by excessive loading from running. Catabolism of the cartilage ECM was defined by the occurrence of degradation of both collagen fibrils and proteoglycans [10] This involves a variety of degradative enzymes, notably matrix metalloproteinases (MMPs), whose basic role is to cleave and initiate the degradation of cartilage components [11]. In this current study, a MMP-3 selective inhibitor was administrated to observe whether it offered a protective effect on cartilage degradation induced by excessive running loading and, subsequent to a further understanding of the roles, whether MMP-3 could have a part in the degradation of cartilage ECM under such mechanical conditions
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