Tendon and ligament injuries are highly prevalent but heal poorly, even with proper care. Restoration of native tissue function is complicated by the fact that these tissues vary anatomically in terms of their mechanical properties, composition, and structure. These differences develop as adaptations to diverse mechanical demands; however, pathology may alter the loads placed on the tissue. Musculoskeletal loads can be generally categorized into tension, compression, and shear. Each of these regulate distinct molecular pathways that are involved in tissue remodeling, including many of the canonical tenogenic genes. In this review, we provide a perspective on the stage-specific regulation of mechanically sensitive pathways during development and maturation of tendon and ligament tissue, including scleraxis, mohawk, and others. Furthermore, we discuss structural features of healing and diseased tendon that may contribute to aberrant loading profiles, and how the associated disturbance in molecular signaling may contribute to incomplete healing or the formation of degenerative phenotypes. The perspectives provided here draw from studies spanning in vitro, animal, and human experiments of healthy and diseased tendon to propose a more targeted approach to advance rehabilitation, orthobiologics, and tissue engineering.

中文翻译：

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利用负荷改善肌腱/韧带组织工程并开发肌腱病的新疗法


肌腱和韧带损伤非常普遍，但即使护理得当，愈合也很差。由于这些组织在机械特性、组成和结构方面的解剖学差异，因此天然组织功能的恢复变得复杂。这些差异随着对不同机械需求的适应而发展;然而，病理学可能会改变施加在组织上的负荷。肌肉骨骼负荷通常可分为拉伸、压缩和剪切。这些中的每一个都调节参与组织重塑的不同分子途径，包括许多经典的肌腱形成基因。在这篇综述中，我们提供了肌腱和韧带组织（包括硬化、莫霍克等）发育和成熟过程中机械敏感通路的阶段特异性调节的观点。此外，我们讨论了可能导致异常负荷曲线的愈合和患病肌腱的结构特征，以及分子信号传导中的相关干扰如何导致不完全愈合或退行性表型的形成。这里提供的观点借鉴了健康和患病肌腱的体外、动物和人体实验，提出了一种更有针对性的方法来推进康复、骨科生物制剂和组织工程。