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Int. J. Mol. Sci. 2017, 18(10), 2199; doi:10.3390/ijms18102199

Time-Dependent Alterations of MMPs, TIMPs and Tendon Structure in Human Achilles Tendons after Acute Rupture

1
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
2
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
*
Author to whom correspondence should be addressed.
Received: 20 September 2017 / Revised: 10 October 2017 / Accepted: 17 October 2017 / Published: 20 October 2017
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

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. View Full-Text
Keywords: tendon healing; human; matrix metalloproteinases; tissue inhibitors of metalloproteinases; ECM composition tendon healing; human; matrix metalloproteinases; tissue inhibitors of metalloproteinases; ECM composition
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Minkwitz, S.; Schmock, A.; Kurtoglu, A.; Tsitsilonis, S.; Manegold, S.; Wildemann, B.; Klatte-Schulz, F. Time-Dependent Alterations of MMPs, TIMPs and Tendon Structure in Human Achilles Tendons after Acute Rupture. Int. J. Mol. Sci. 2017, 18, 2199.

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