Mechanisms of tenocyte mechanotransduction

肌腱连接肌肉和骨骼；它们的独特设计可以承受由重复的肌肉活动产生的高拉伸负荷。在肌肉骨骼组织中，肌腱对机械刺激(机械转导)的生物反应性相对较少。肌腱由腱细胞组成，是一种专门的成纤维细胞，能产生高水平的I型胶原(由col1a1基因编码，其启动子在肌腱中由转录因子skerAxis-SCx调节)。就像肌肉或骨骼一样，肌腱可以安装对运动的适应性反应，这可能取决于负荷参数。然而，不同的拉伸参数对COL1a1及其相关基因表达水平的影响还没有得到充分的研究。我的初步数据显示，在体外肌腱细胞的周期性(相对于静态)拉伸负荷下，col1a1和肌腱特异的调节转录因子(SCx和tnmd)上调，并且这些反应通过在负荷周期之间插入休止期而增强。这个研究计划的主要目标是通过在体外和体内施加不同的加载方式来加深我们对基本肌腱生物学的理解，并检查(1)对承载胶原基质的结构和功能的影响，(2)支持这些影响的机制(机械转导途径)。这些结果将促进我们对肌腱生物学的理解，并将作为未来应用研究途径的基础，例如比较不同运动方式对肌腱力学性能的影响。

Tendons connect muscles to bone; they are uniquely designed to withstand high tensile loads generated by repetitive muscle activity. Among musculoskeletal tissues, tendon's biological responsiveness to mechanical stimulation (mechanotransduction) is relatively unexplored. Tendons are populated by tenocytes, specialized fibroblasts which produce high levels of Type I collagen (encoded by col1a1 mRNA, a gene whose promoter is regulated in tendon by a transcription factor, scleraxis - scx). Like muscle or bone, tendon can mount adaptive responses to movement which are likely to be dependent on the load parameters. However, the effect of varying tensile parameters on the expression levels of col1a1 and related genes has not been fully explored. My pilot data shows that col1a1 and tendon-specific regulatory transcription factors (scx and tnmd) are upregulated in response to cyclic (as compared to static) tensile loading of tendon cells in vitro, and that these responses are enhanced by the insertion of rest-periods between loading cycles. The broad goal of this research program is to further our understanding of basic tendon biology by applying varying loading regimes in vitro and in vivo, and examining (1) the effect on the structure and function of the load-bearing collagen matrix, and (2) the mechanisms (mechanotransduction pathways) which underpin these effects. The results will accelerate our understanding of tendon biology and will serve as the future basis for applied research avenues, e.g. comparing the effects of different modes of exercise on tendon mechanical properties.