BACKGROUND Spontaneous Achilles tendon rupture associated with long-term dexamethasone (Dex) use has been reported. However, few studies have investigated the potential mechanism. The aim of this study was to evaluate the effects of oral Dex on type I collagen in humans and rats and its association with tendon rupture. METHODS First, six Achilles tendons from patients who received long-term Dex treatment, and another six normal tendons were harvested for histological evaluation. Secondly, 8-week-old rats (n = 72) were randomly assigned to a Dex group or a control group. Type I collagen was studied at the mechanical, histological, and molecular levels after 3 and 5 weeks. Tenocytes isolated from normal human and rat tendon were used to investigate the effect of Dex on cellular scale. RESULTS Histological analysis of human and rat tendon tissue revealed an irregular, disordered arrangement of type I collagen in the Dex group compared with the control group. In addition, In the Dex+ group, type I collagen expression decreased in comparison with the Dex- group in both human and rat tenocytes. The mechanical strength of tendons was significantly reduced in the Dex group (68.87 ± 11.07 N) in comparison with the control group (81.46 ± 7.62 N, P = 0.013) after 5 weeks. Tendons in the Dex group were shorter with smaller cross-sectional areas (10.71 ± 0.34 mm2, 1.44 ± 0.22 mm2, respectively) after 5 weeks than those in the control group (11.13 ± 0.50 mm2, P = 0.050, 2.74 ± 0.34 mm2, P < 0.001, respectively). CONCLUSIONS This finding suggests long-term use of Dex that decreases the expression of type I collagen at molecular and tissue levels both in human and rat Achilles tendons. Furthermore, Dex decreases the mechanical strength of the tendon, thereby increasing the risk of Achilles tendon rupture.

中文翻译：

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地塞米松对跟腱中I型胶原表达的下调：一项对照实验室研究。

背景技术已经报道了与长期地塞米松（Dex）使用相关的自发性跟腱断裂。但是，很少有研究调查潜在的机制。这项研究的目的是评估口服Dex对人和大鼠I型胶原蛋白的作用及其与肌腱断裂的关系。方法首先，从接受长期Dex治疗的患者中获得6个跟腱，并再收集6个正常肌腱进行组织学评估。其次，将8周龄大鼠（n = 72）随机分为Dex组或对照组。在3周和5周后，研究了I型胶原的力学，组织学和分子水平。从正常人和大鼠肌腱分离的肌腱细胞用于研究Dex对细胞规模的影响。结果人和大鼠肌腱组织的组织学分析显示，与对照组相比，Dex组的I型胶原蛋白排列不规则，无序。另外，在Dex +组中，人和大鼠肌腱细胞中的I型胶原蛋白表达均与Dex-组相比降低。5周后，与对照组相比（81.46±7.62 N，P = 0.013），Dex组的肌腱机械强度显着降低（68.87±11.07 N）。5周后，Dex组的肌腱较短，截面积较小（分别为10.71±0.34 mm2，1.44±0.22 mm2），而对照组则为（11.13±0.50 mm2，P = 0.050，2.74±0.34 mm2，分别为P <0.001）。结论该发现表明，长期使用Dex可以降低人和大鼠跟腱的分子和组织水平的I型胶原蛋白的表达。此外，Dex降低了肌腱的机械强度，从而增加了跟腱断裂的风险。