Regulatory mechanism of the extracellular matrix during the development of bone-tendon junction overuse injury / 中国组织工程研究

ABSTRACT

BACKGROUND: Overuse tendinopathy is a common disease with no ideal treatment because the pathogenesis of tendinopathy is still unclear. OBJECTIVE: To explore the effects of enzymes affecting collagen synthesis on the metabolism of collagen I and collagen III during load accumulation in a model of patella-patellar tendon junction overuse injury. METHODS: Thirty-two adult female New Zealand white rabbits were randomly divided into a jumping group (n=16) and a control group (n=16). In the jump group, rabbits were subjected to jump training for 2, 4, 6, and 8 weeks, 150 jumps per day, 5 days per week. No intervention was performed in the control group. Bilateral patella-patellar tendon junction samples were taken at 24 hours after 2-, 4-, 6-, and 8- week training. The time-series changes of matrix metalloproteinase 1 (MMP1), tissue inhibitor of metalloproteinase 1 (TIMP1), collagen I, and collagen III were measured by immunohistochemistry. The study was performed with an ethic approval from the Animal Ethical Committee of Beijing Sport University, China (approval No. BSU2015022). RESULTS AND CONCLUSION: Compared with the control group, the MMP1 activity was significantly lower within the first 6 weeks of training, TIMP1 activity was significantly higher at 4-8 weeks of training, and TIMP1/MMP1 was significantly higher at 4-8 weeks of training. Compared with the control group, the expression of collagen I was significantly increased in the first 6 weeks of training, but the expression of collagen III was significantly lowered after 8 weeks of training. TIMP1 activity was significantly positively correlated with collagen I expression, and MMP1 activity was significantly negatively correlated with collagen I expression. To conclude, the patella-patellar tendon junction, during jumping load accumulation, mainly responded to load stimulation by increasing collagen I expression. In the first 2 weeks of load accumulation, the expression of collagen I was mainly increased by inhibiting MMP1 activity; in the period of 4 to 6 weeks of load accumulation, the expression of collagen I was mainly increased by increasing the activity of TIMP1 and inhibiting the activity of MMP1; and after 8 weeks of load accumulation, TIMP1 could promote collagen synthesis but with inability to antagonize the degradation of collagen I and III by MMP1. Then the expression of collagen I decreased from the peak level after 6 weeks of training to the control group level, and the level of collagen III decreased to be less than the level of the control group.