Mechanical loading regulates the expression of tenascin-C in the myotendinous junction and tendon but does not induce de novo synthesis in the skeletal muscle
Mechanical loading regulates the expression of tenascin-C in the myotendinous junction and tendon but does not induce de novo synthesis in the skeletal muscle
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DOI：
10.1242/jcs.00303
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发表时间：
2003-03-01
影响因子：
4
通讯作者：
Järvinen, M
中科院分区：
文献类型：
--
作者：
Järvinen, TAH;Józsa, L;Järvinen, M
腱生蛋白-C是一种六臂形的基质细胞蛋白，在正常肌肉骨骼组织中表达非常有限，但在这些组织的再生过程和胚胎发生中大量表达。为了研究机械应力对肌肉-肌腱单元中腱生蛋白-C表达调节的重要性，各种机械载荷状态的影响采用免疫组织化学和mRNA原位杂交技术研究了不同强度的石膏固定（不活动）和随后的三种不同强度的跑步机运动对腱生蛋白-C表达的影响。大鼠腓肠肌的肌腱单位，跟腱复合体。由于腓肠肌-比目鱼肌复合体的收缩活动以及由此引起的机械负荷引起的刺激容易被管型固定所阻断，因此选择该肌肉-肌腱单位作为研究部位。腱蛋白-C在正常的肌腱和肌筋膜连接处以及跟腱的细胞和胶原纤维周围大量表达。在正常骨骼肌中未发现腱生蛋白-C表达，尽管在肌肉组织内的血管中发现了腱生蛋白-C表达。通过石膏固定3周去除对肌肉-肌腱单元的机械负荷诱导的刺激后，在正常表达腱生蛋白-C的区域中腱生蛋白-C的免疫反应性显著降低或完全不存在。通过移除石膏并允许自由笼活动8周来恢复机械负荷导致腱生蛋白-C表达增加，但其不能将腱生蛋白-C的表达恢复到正常水平（在健康对侧腿中）。为了响应在移除石膏后施加更剧烈的机械负荷刺激（在低强度和高强度跑步机跑步8周后），腱生蛋白-C的表达显著增加，并达到在健康对侧肢体中观察到的水平。肌腱蛋白-C在肌腱和肌筋膜连接处和跟腱中大量表达，但即使是最剧烈的机械负荷（高强度跑步机跑步）也不能诱导肌腱蛋白-C在骨骼肌中的表达。这是尽管显着的固定诱导萎缩的先前固定的骨骼肌，这已受到强烈的压力，在重新动员。mRNA原位杂交分析证实了免疫组化结果的表达tenascin-C的研究groups.In总结，这项研究表明，机械负荷调节tenascin-C的表达在一个明显的剂量依赖性的方式在网站的肌肉肌腱单位正常表达tenascin-C，但不能诱导从头合成tenascin-C在骨骼肌中没有伴随损伤的组织。我们的研究结果表明，腱生蛋白-C提供了弹性间充质组织进行重拉伸负荷。
Tenascin-C is a hexabrachion-shaped matricellular protein with a very restricted expression in normal musculoskeletal tissues, but it is expressed abundantly during regenerative processes of these tissues and embryogenesis. To examine the importance of mechanical stress for the regulation of tenascin-C expression in the muscle-tendon unit, the effects of various states of mechanical loading (inactivity by cast-immobilization and three-varying intensities of subsequent re-activity by treadmill running) on the expression of tenascin-C were studied using immunohistochemistry and mRNA in situ hybridization at the different locations of the muscle-tendon unit of the rat gastrocnemius muscle, the Achilles tendon complex. This muscle-tendon unit was selected as the study site, because the contracting activity of the gastrocnemius-soleus muscle complex, and thus the mechanical loading-induced stimulation, is easy to block by cast immobilization.Tenascin-C was expressed abundantly in the normal myotendinous and myofascial junctions, as well as around the cells and the collagen fibers of the Achilles tendon. Tenascin-C expression was not found in the normal skeletal muscle, although it was found in blood vessels within the muscle tissue. Following the removal of the mechanical loading-induced stimulation on the muscle-tendon unit by cast immobilization for 3 weeks, the immonoreactivity of tenascin-C substantially decreased or was completely absent in the regions expressing tenascin-C normally. Restitution of the mechanical loading by removing the cast and allowing free cage activity for 8 weeks resulted in an increase in tenascin-C expression, but it could not restore the expression of tenascin-C to the normal level (in healthy contralateral leg). In response to the application of a more strenuous mechanical loading stimulus after the removal of the cast (after 8 weeks of low- and high-intensity treadmill running), the expression of tenascin-C was markedly increased and reached the level seen in the healthy contralateral limb. Tenascin-C was abundantly expressed in myotendinous and myofascial junctions and in the Achilles tendon, but even the most strenuous mechanical loading (high-intensity treadmill running) could not induce the expression of tenascin-C in the skeletal muscle. This was in spite of the marked immobilization-induced atrophy of the previously immobilized skeletal muscle, which had been subjected to intensive stress during remobilization. mRNA in situ hybridization analysis confirmed the immunohistochemical results for the expression of tenascin-C in the study groups.In summary, this study shows that mechanical loading regulates the expression of tenascin-C in an apparently dose-dependent fashion at sites of the muscle-tendon unit normally expressing tenascin-C but can not induce de novo synthesis of tenascin-C in the skeletal muscle without accompanying injury to the tissue. Our results suggest that tenascin-C provides elasticity in mesenchymal tissues subjected to heavy tensile loading.