Lin Tony W, Cardenas Luis, Soslowsky Louis J
McKay Orthopaedic Research Laboratory, University of Pennsylvania, 424 Stemmler Hall, 36th and Hamilton walk, Philadelphia, PA 19104-6081, USA.
J Biomech. 2005 Jan;38(1):99-105. doi: 10.1016/j.jbiomech.2004.03.008.
Cytokines are known to play an important role in normal tendon development, function, and maintenance through interactions with fibroblasts and extracellular matrix proteins. However, the role of interleukins on normal tendon activity remains poorly understood. Previous studies that have researched the role of specific cytokines by exogenously applying them have often reported conflicting results. Therefore, a knockout mouse model was used to investigate the role of interleukins 4 and 6 on normal tendon organizational and biomechanical properties. It was hypothesized that interleukin-6 knockout (IL6 -/-) mice will display more organized collagen orientation and greater cross-sectional area and mechanical properties when compared to that of control mice. In addition, interleukin-4 knockout (IL4 -/-) mice will display the most disorganized collagen orientation and lowest cross-sectional area and mechanical properties. As hypothesized, IL6 -/- mice show a trend towards lower angular deviation (more organized) (p<0.1) when compared to IL4 -/- mice. In addition, the IL6 -/- mice show a trend towards a higher percent relaxation (p<0.1) and a significantly higher modulus (p<0.01) when compared to CTL and IL4 -/- mice. Unexpectedly, the IL6 -/- mice exhibited no significant differences in collagen fiber distribution and maximum stress from the other groups and actually had a smaller cross-sectional area than CTL mice (p<0.1). This study supports transgenic mice as an animal model for investigating how cytokines affect normal tendon properties. In addition, this study demonstrates that interleukins may play an important role in tendon development, function, and maintenance.
已知细胞因子通过与成纤维细胞和细胞外基质蛋白相互作用，在正常肌腱发育、功能及维持中发挥重要作用。然而，白细胞介素对正常肌腱活动的作用仍知之甚少。以往通过外源性应用特定细胞因子来研究其作用的研究常常报道相互矛盾的结果。因此，本研究使用基因敲除小鼠模型来探究白细胞介素4和6对正常肌腱组织学和生物力学特性的作用。研究假设，与对照小鼠相比，白细胞介素-6基因敲除（IL6-/-）小鼠将表现出更有序的胶原纤维排列方向、更大的横截面积以及更好的力学性能。此外，白细胞介素-4基因敲除（IL4-/-）小鼠将表现出最无序的胶原纤维排列方向、最小的横截面积以及最差的力学性能。正如所假设的，与IL4-/-小鼠相比，IL6-/-小鼠呈现出角偏差降低（更有序）的趋势（p<0.1）。此外，与CTL和IL4-/-小鼠相比，IL6-/-小鼠呈现出更高的松弛百分比趋势（p<0.1）以及显著更高的模量（p<0.01）。出乎意料的是，IL6-/-小鼠在胶原纤维分布和最大应力方面与其他组相比无显著差异，且其横截面积实际上比CTL小鼠更小（p<0.1）。本研究支持将转基因小鼠作为研究细胞因子如何影响正常肌腱特性的动物模型。此外，本研究表明白细胞介素可能在肌腱发育、功能及维持中发挥重要作用。
