Tendon healing in interleukin-4 and interleukin-6 knockout mice

Tendon healing in interleukin-4 and interleukin-6 knockout mice
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DOI:
10.1016/j.jbiomech.2004.11.009
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发表时间:
2006-01-01
影响因子:
2.4
通讯作者:
Soslowsky, LJ
Soslowsky, LJ
中科院分区:
工程技术3区
文献类型:
--
作者:
Lin, TW;Cardenas, L;Soslowsky, LJ

文献摘要

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细胞因子通过调节细胞分化和活性在肌腱和韧带愈合中发挥重要作用。大多数研究细胞因子在肌腱和韧带愈合中的作用的研究都将它们添加到受伤的组织中并评估其效果。由于外源性应用细胞因子的疗效取决于许多因素,如正确的剂量,时间和频率,经常报告相互矛盾的结果。为了避免这些因素,本研究使用敲除白细胞介素-4(IL-4-/-)和白细胞介素-6(116 -/-)的转基因小鼠来研究它们在肌腱愈合中的作用。由于这两种细胞因子在炎症和纤维组织增生中的作用,假设组织、几何和机械性质的顺序为(最大到最小)损伤的IL 6-/-、损伤的对照和损伤的IL 4-/-小鼠。此外,假设特异性细胞因子在每个敲除组中上调,但不能补偿IL-4或IL-6的缺乏。尽管促炎细胞因子TNF-α上调,但IL 6-/-小鼠的损伤肌腱的机械和组织特性劣于对照和IL 4-/-小鼠。当与CTL小鼠相比时,IL-4-/-小鼠中IL- 10和IL- 13的时间水平导致相当的甚至上级的性质。这项研究表明,IL-6不能得到补偿,并在肌腱愈合中发挥重要作用。这项研究也支持使用这种动物模型来进一步研究肌腱愈合。(c)2004爱思唯尔有限公司保留所有权利。
Cytokines have been shown to play an important role in tendon and ligament healing by regulating cellular differentiation and activity. The majority of studies that have investigated the role of cytokines in tendon and ligament healing have added them to injured tissue and assessed their effect. Because the efficacy of exogenously applying cytokines is dependent upon many factors such as the correct dosage, timing, and frequency, conflicting results are often reported. To avoid these factors, this study used transgenic mice with knockouts of interleukin-4 (IL4 -/-) and interleukin-6 (116 -/-) to investigate their role in tendon healing. Because of the reported roles of both of these cytokines in inflammation and fibroplasia, it was hypothesized that the order of organizational, geometric, and mechanical properties would be (greatest to least) injured IL6 -/-, injured control, and injured IL4 -/- mice. In addition, it was hypothesized that specific cytokines would be upregulated in each knockout group, but not compensate for the lack of IL-4 or IL-6. Mechanical and organizational properties of injured tendons from IL6 -/- mice were inferior to that of control and IL4 -/- mice despite the upregulation of the pro-inflammatory cytokine TNF-alpha. Temporal levels of IL- 10 and IL- 13 in the IL4 -/- mice resulted in comparable and even superior properties when compared to CTL mice. This study shows that IL-6 could not be compensated for and plays an important role in tendon healing. This study also supports the use of this animal model to further investigate tendon healing. (c) 2004 Elsevier Ltd. All rights reserved.