Matrix metalloproteinase inhibitors prevent a decrease in the mechanical properties of stress-deprived tendons - An in vitro experimental study
Matrix metalloproteinase inhibitors prevent a decrease in the mechanical properties of stress-deprived tendons - An in vitro experimental study
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DOI：
10.1177/0363546506296043
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发表时间：
2007-05-01
影响因子：
4.8
通讯作者：
Gardner, Keri
中科院分区：
文献类型：
--
作者：
Arnoczky, Steven P.;Lavagnino, Michael;Gardner, Keri
背景资料：基质金属蛋白酶（MMPs）的增加和由此导致的细胞外基质的降解与肌腱病的发病机制有关。研究已经证明了MMP抑制剂用于治疗MMP活性对结缔组织有负面影响的病理状况的有益效果。假设：基质金属蛋白酶抑制剂将通过抑制MMP活性来防止与肌腱应力剥夺相关的材料性质的降低。研究设计：对照实验室研究。方法：大鼠尾腱进行7天的体外应力剥夺，并添加和不添加1的2个广谱MMP抑制剂（多西环素和伊洛马司他）。材料性能（极限拉伸应力，应变和拉伸模量）的钢筋束进行了比较，彼此和新鲜的控制钢筋束。此外，从每组肌腱进行了评估MMP-13信使RNA表达，MMP-13蛋白合成，MMP-13活性，和pericellular matrix morphology.Results：两个MMP抑制剂导致在统计学上显着减少MMP活性在7天的应力剥夺肌腱相比，未经处理，应力剥夺肌腱。同样，用伊洛马司他或多西环素处理的肌腱具有显著改善的材料性质。MMP-13信使RNA的表达和蛋白质合成没有显着影响MMP抑制剂。两种MMP抑制剂都能够维持细胞周围基质的完整性时，与未经处理，应力剥夺tendons.Conclusion：基质金属蛋白酶抑制剂阻止MMP-13的激活，并显着抑制细胞周围基质变性和材料性能的损失与应力剥夺。基质金属蛋白酶抑制剂可能通过限制MMP介导的细胞外基质降解而在肌腱病变的治疗中发挥支持作用。
Background: An increase in matrix metalloproteinases (MMPs) and the resulting degradation of the extracellular matrix have been implicated in the pathogenesis of tendinopathy. Studies have documented the beneficial effects of MMP inhibitors used to treat pathologic conditions in which MMP activity has had a negative effect on connective tissues.Hypothesis: Matrix metalloproteinase inhibitors will prevent the decrease in material properties associated with tendon stress deprivation by inhibiting MMP activity.Study Design: Controlled laboratory study.Methods: Rat tail tendons were subjected to 7 days of in vitro stress deprivation with and without the addition of 1 of 2 broad-spectrum MMP inhibitors (doxycycline and ilomastat). The material properties (ultimate tensile stress, strain, and tensile modulus) of the tendons were compared with each other and with fresh control tendons. In addition, tendons from each group were evaluated for MMP-13 messenger RNA expression, MMP-13 protein synthesis, MMP-13 activity, and pericellular matrix morphology.Results: Both MMP inhibitors resulted in a statistically significant reduction in MMP activity in 7 day stress-deprived tendons when compared with nontreated, stress-deprived tendons. Similarly, tendons treated with either ilomastat or doxycycline had significantly improved material properties. MMP-13 messenger RNA expression and protein synthesis were not significantly affected by either MMP inhibitor. Both MMP inhibitors were able to maintain the integrity of the pericellular matrix when compared with nontreated, stress-deprived tendons.Conclusion: Matrix metalloproteinase inhibitors prevented the activation of MMP-13 and significantly inhibited pericellular matrix degeneration and the loss of material properties associated with stress deprivation.Clinical Relevance: Matrix metalloproteinase inhibitors may play a supportive role in the treatment of tendinopathy by limiting the MMP-mediated degradation of the extracellular matrix.