Mechanisms of tenocyte mechanotransduction

肌腱连接肌肉和骨骼；它们的独特设计可以承受重复性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）的生物反应性相对未被探索。肌腱由腱细胞填充，这种特化的成纤维细胞产生高水平的I型胶原（由col1a1 mRNA编码，该基因的启动子在肌腱中受转录因子scleraxis - scx调节）。像肌肉或骨骼一样，肌腱可以对运动产生适应性反应，这可能取决于负载参数。然而，不同拉伸参数对col1a1及相关基因表达水平的影响尚未得到充分探讨。我的实验数据表明，col1a1和肌腱特异性调节转录因子（scx和tnmd）在体外对肌腱细胞的周期性（与静态）拉伸载荷的反应中上调，并且这些反应通过在加载周期之间插入休息期而增强。本研究计划的广泛目标是通过在体外和体内应用不同的负荷制度，并检查(1)对承重胶原基质的结构和功能的影响，以及(2)支撑这些影响的机制（机械转导途径），进一步加深我们对基本肌腱生物学的理解。这些结果将加速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，例如比较不同运动模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.