Enhancement of Achilles Tendon Repair Mediated by Matrix Metalloproteinase Inhibition via Systemic Administration of Doxycycline
Enhancement of Achilles Tendon Repair Mediated by Matrix Metalloproteinase Inhibition via Systemic Administration of Doxycycline
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DOI：
10.1002/jor.22564
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发表时间：
2014-04-01
影响因子：
2.8
通讯作者：
Chahine, Nadeen O.
中科院分区：
文献类型：
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作者：
Kessler, Michael W.;Barr, Jerome;Chahine, Nadeen O.
胶原酶或基质金属蛋白酶（MMPs）已被证明在与跟腱断裂和疾病相关的基质降解级联反应中发挥重要作用。本研究的目的是研究每日口服强力霉素（Doxy）对MMP活性和跟腱修复质量的影响。我们的研究结果表明，跟腱横断导致增加MMP-8活性从2至6周后受伤，峰值增加的活动发生在4周后受伤。发现临床相关血清浓度的Doxy给药在连续治疗4周后显著抑制MMP活性，但对于较短持续时间（96小时或2周）的连续给药则没有。延长DOXY给药也与改善胶原纤维组织和增强生物力学性能（刚度、极限拉伸强度、最大失效载荷和弹性韧性）相关。我们的研究结果表明跟腱横断和原位MMP-8活性相关增加之间存在时间延迟。我们的研究结果表明，抑制MMP-8在其峰值活性水平改善纤维化的发展，并改善跟腱的生物力学性能。(c)2013年骨科研究学会。由威利期刊公司出版J Orthop Res 32：500-506，2014.
Collagenases or matrix metalloproteinases (MMPs) have been shown to play an important role in the matrix degradation cascade associated with Achilles tendon rupture and disease. The goal of this study was to examine the effects of daily administration of doxycycline (Doxy) through oral gavage on MMP activity and on the repair quality of Achilles tendons in vivo. Our findings indicate that Achilles tendon transection resulted in increasing MMP-8 activity from 2 to 6 weeks post-injury, with peak increases in activity occurring at 4 weeks post-injury. Doxy adiministration at clinically relevant serum concentrations was found to significantly inhibit MMP activity after continuous treatment for 4 weeks, but not for continuous administration for shorter durations (96h or 2 weeks). Extended doxy administration was also associated with improved collagen fibril organization, and enhanced biomechanical properties (stiffness, ultimate tensile strength, maximum load to failure, and elastic toughness). Our findings indicate that a temporal delay exists between Achilles tendon transection and associated increases in MMP-8 activity in situ. Our findings suggest that inhibition of MMP-8 at its peak activity levels ameliorates fibrosis development and improves biomechanical properties of the Achilles tendon. (c) 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:500-506, 2014.