肌腱损伤是肌骨系统伤病中最常见的一种，其会引起疼痛，影响病人的日常生活,严重的话会导致残疾。在课题组前期研究中，我们首次发现了AKT通过将力学刺激信号转化成生物信号调节了肌腱组织的形成。于是我们针对AKT活化所需的上游激酶PDK1，构建了肌腱特异性PDK1基因敲除小鼠（SCX-PDK1）模型。在成年SCX-PDK1小鼠中，我们发现虽然其跟腱比野生型小鼠要小，但是并没有明显的行动障碍。值得注意的是，SCX-PDK1小鼠在仅仅接受低强度的跑步机训练后，就发生了跟腱变小和断裂的情况，而野生型小鼠却没有任何异常。基于前期研究基础，我们假设PDK1/AKT的激活是肌腱细胞转译力学信号的重要节点，其对肌腱的形成与力学保护其重要的作用。为了验证我们的假设，本项目拟结合体外基础研究和转基因小鼠体内模型，对肌腱受力保护机制进行深入的研究，为未来肌腱研究奠定基础和对肌腱损伤的治疗提供新的思路。

Tendons are mechanosensitive connective tissues that transfer force from muscle to bone. Although mechanical overload is one of the main causes of tendon injuries, physiological loading still plays an essential role in maintaining tendon integrity. In China, a huge health and economy burden is caused by tendon injuries. Therefore, better strategies are needed in tendon injury prevention, treatment development and rehabilitation. To achieve this goal, the fundamental understanding of how tendons maintain homeostasis subjected to mechanical stimulation is essential. In our previous studies, we identified that activation AKT signal cascade by the 6% uni-axial loading, plays an essential role in the tenogenesis and neo-tendon formation. Thus, we generated SCX-PDK1 mice strain with compromised AKT activation in tendon tissue, and demonstrated for the first time that even low-intensity treadmill training induced decreased tendon mass and rupture of Achilles tendon in SCX-PDK1 mice but not in WT mice. Based on our preliminary findings, we hypothesize that “PDK1/AKT signaling pathway is essential in maintaining homeostasis of tendon subjected to mechanical loading”. To address the hypothesis, we will execute the following four linked AIMs:.AIM 1: Investigate the role of PDK1/AKT activation in tendon development, maturation and in vitro neo-tendon formation ability using SCX-PDK1 mice. .AIM 2: Examine if transgenic inducible deletion of PDK1 impair tendon homeostasis subjected to mechanical overloading using tendon specific tamoxifen-inducible deletion PDK1 mice model (SCX-CreER-PDK1)..AIM 3: Investigate whether pharmacological manipulation of AKT activation improves tendon healing in tendon injury mice model..This project will provide a powerful tool for the further basic tendon study and possibly form the foundation on which to build future research into the development of novel strategies or refinement of existing pharmacological interventions for tendon health.