Tenomodulin is Required for Tendon Endurance Running and Collagen I Fibril Adaptation to Mechanical Load.
Tenomodulin is Required for Tendon Endurance Running and Collagen I Fibril Adaptation to Mechanical Load.
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DOI：
10.1016/j.ebiom.2017.05.003
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发表时间：
2017-06
期刊：
影响因子：
11.1
通讯作者：
Docheva D
中科院分区：
文献类型：
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作者：
Dex S;Alberton P;Willkomm L;Söllradl T;Bago S;Milz S;Shakibaei M;Ignatius A;Bloch W;Clausen-Schaumann H;Shukunami C;Schieker M;Docheva D
肌腱是将肌肉附着在骨骼上的致密结缔组织，由于其储存和释放肌肉产生的弹性能的内在特性，在运动中发挥着不可或缺的作用。肌腱调节蛋白 (Tnmd) 是一种公认的成熟肌腱/韧带谱系基因标记物，其在小鼠体内的功能丧失会导致组织和干细胞/祖细胞水平上出现明显过早衰老迹象的表型。基于这些发现，我们假设 Tnmd 可能是肌腱功能表现的一个重要因素。首先，我们揭示了 Tnmd 是一种机械敏感基因，并且该蛋白的 C 末端与细胞外基质中的 I 型胶原纤维共定位。其次，使用耐力训练方案，我们将 Tnmd 敲除小鼠与野生型小鼠进行比较，结果表明 Tnmd 缺陷导致跑步表现明显较差，并且随着训练进一步恶化。在这些小鼠中，由于I型胶原交联和蛋白聚糖基因的异常反应导致I型胶原纤维厚度和弹性不足，耐力跑受到阻碍。总之，我们的研究表明 Tnmd 是肌腱组织适当适应耐力跑所必需的，并有助于更好地理解肌腱组织的结构功能关系。 Tnmd 是一种机械敏感基因，其蛋白质与肌腱 ECM 中的 I 型胶原纤维共定位。 Tnmd 基因敲除小鼠在耐力跑测试中失败，这种表型会随着训练而恶化。 Tnmd 敲除肌腱具有明显更厚、更硬的 I 型胶原纤维，并且改变了交联基因表达。我们采用多学科方法来解读肌腱调节蛋白（成熟肌腱谱系的基因标记物）在肌腱功能表现中的作用。小鼠功能丧失导致耐力跑明显较差，详细分析表明，腱调节蛋白参与调节 I 型胶原蛋白纤维结构和生物力学特性以响应运动。我们的研究扩展了目前对肌腱组织复杂的结构功能关系的看法，腱调节蛋白的表达水平可能表明一个人是否适合某种运动。
Tendons are dense connective tissues that attach muscles to bone with an indispensable role in locomotion because of their intrinsic properties of storing and releasing muscle- generated elastic energy. Tenomodulin (Tnmd) is a well-accepted gene marker for the mature tendon/ligament lineage and its loss-of -function in mice leads to a phenotype with distinct signs of premature aging on tissue and stem/progenitor cell levels. Based on these findings, we hypothesized that Tnmd might be an important factor in the functional performance of tendons. Firstly, we revealed that Tnmd is a mechanosensitive gene and that the C-terminus of the protein co-localize with collagen I-type fibers in the extracellular matrix. Secondly, using an endurance training protocol, we compared Tnmd knockout mice with wild types and showed that Tnmd deficiency leads to significantly inferior running performance that further worsens with training. In these mice, endurance running was hindered due to abnormal response of collagen I cross-linking and proteoglycan genes leading to an inadequate collagen I fiber thickness and elasticity. In sum, our study demonstrates that Tnmd is required for proper tendon tissue adaptation to endurance running and aids in better understanding of the structural-functional relationships of tendon tissues. Tnmd is a mechanosensitive gene and its protein is co-localized with collagen I fibers in the ECM of tendons. Tnmd knockout mice fail in endurance running tests, a phenotype that worsens with training. Tnmd knockout tendons had significantly thicker and stiffer collagen I fibers and altered crosslinking gene expression. We performed a multidisciplinary approach to decipher the role of tenomodulin, a gene marker for the mature tendon lineage, in tendon functional performance. Loss-of-function in mice led to significantly inferior endurance running and detailed analyses revealed that tenomodulin is involved in the regulation of collagen I fiber structural and biomechanical properties in response to exercise. Our study expands the current view on the complex structural-functional relationships of tendon tissues, and tenomodulin expression levels may indicate whether an individual is suitable for a certain sport.