Julius Wolff Institute, Center for Musculoskeletal Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, Germany.
Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, Germany.
Int J Mol Sci. 2017 Oct 20;18(10):2199. doi: 10.3390/ijms18102199.
A balance between matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) is required to maintain tendon homeostasis. Variation in this balance over time might impact on the success of tendon healing. This study aimed to analyze structural changes and the expression profile of MMPs and TIMPs in human Achilles tendons at different time-points after rupture. Biopsies from 37 patients with acute Achilles tendon rupture were taken at surgery and grouped according to time after rupture: early (2-4 days), middle (5-6 days), and late (≥7 days), and intact Achilles tendons served as control. The histological score increased from the early to the late time-point after rupture, indicating the progression towards a more degenerative status. In comparison to intact tendons, qRT-PCR analysis revealed a significantly increased expression of MMP-1, -2, -13, TIMP-1, COL1A1, and COL3A1 in ruptured tendons, whereas TIMP-3 decreased. Comparing the changes over time post rupture, the expression of MMP-9, -13, and COL1A1 significantly increased, whereas MMP-3 and -10 expression decreased. TIMP expression was not significantly altered over time. MMP staining by immunohistochemistry was positive in the ruptured tendons exemplarily analyzed from early and late time-points. The study demonstrates a pivotal contribution of all investigated MMPs and TIMP-1, but a minor role of TIMP-2, -3, and -4, in the early human tendon healing process.
基质金属蛋白酶（MMPs）与其抑制剂（TIMPs）之间需要保持平衡，以维持肌腱的内稳态。这种平衡随时间的变化可能会影响肌腱愈合的成功率。本研究旨在分析人跟腱断裂后不同时间点 MMPs 和 TIMPs 的结构变化和表达谱。对 37 例急性跟腱断裂患者的手术标本进行活检，并根据断裂后时间进行分组：早期（2-4 天）、中期（5-6 天）和晚期（≥7 天），正常跟腱作为对照。组织学评分从早期到晚期逐渐增加，表明向更退行性状态的进展。与正常肌腱相比，qRT-PCR 分析显示断裂肌腱中 MMP-1、-2、-13、TIMP-1、COL1A1 和 COL3A1 的表达显著增加，而 TIMP-3 减少。比较断裂后随时间的变化，MMP-9、-13 和 COL1A1 的表达显著增加，而 MMP-3 和 -10 的表达减少。TIMP 表达随时间无显著变化。免疫组织化学染色显示 MMP 在早期和晚期的断裂肌腱中呈阳性。该研究表明，所有研究的 MMPs 和 TIMP-1 在早期人类肌腱愈合过程中都有重要贡献，但 TIMP-2、-3 和 -4 的作用较小。
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