title: Matrix metalloproteinase-3 inhibitor retards treadmill running-induced cartilage degradation in rats.
abstract: BACKGROUND
  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.
  
  
  METHODS
  A 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.
  
  
  RESULTS
  Histological 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.
  
  
  CONCLUSIONS
  High-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.
authors: Department of Orthopeadics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou Road 1838, 510515, Guangzhou, China. fgxni@graduate.hku.hk
authors: Guo-Xin
authors: GX
authors: Ni
authors: Li-Qiong
authors: LQ
authors: Zhan
authors: Mei-Qin
authors: MQ
authors: Gao
authors: Lei
authors: L
authors: Lei
authors: Yue-Zhu
authors: YZ
authors: Zhou
authors: Yan-Xia
authors: YX
authors: Pan
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005080:Exercise Test; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007150:Immunohistochemistry; D007270:Injections, Intra-Articular; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012420:Running; D013997:Time Factors
chemical_list: D024043:Collagen Type II; D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D019278:Matrix Metalloproteinase 3