TENDON CELLS:INTERACTIONS & RESPONSES TO STRESS IN VITRO

描述（改编自申请人的摘要）：细胞间 沟通对于大多数器官的自我平衡功能至关重要， 协调发育过程中的事件，以及心脏收缩的速度， 肺、肠、勃起组织和子宫。发表了校长的报告 研究小组现在指出，细胞活动协调 在屈肌腱对机械负荷的反应中，通过缝隙连接是至关重要的 和伤害。运动对维持健康至关重要：正常活动 积极的，固定是消极的，过度活跃是破坏性的。在 在医学上，运动疗法对恢复运动范围至关重要。 申请人假设通过间隙的细胞活动的协调 关节在应对机械负荷和肌腱损伤后至关重要。如果 缝隙连接被阻断，细胞协调将被阻止。具体目标 1，他们将测试间隙连接在通过Ca 2+，间隙连接 用GFP-cx43构建体以及DNA和胶原连接易位 在体外已经机械加载和受伤的细胞中的合成+/- 缝隙连接阻塞。负荷将包括急性和适应性方案。 在具体目标2中，他们将测试PKC调节对间隙连接的影响。 表达和功能的化合物，如ATP和去甲肾上腺素， 调节缝隙连接信号传导和表达。在具体目标3和4中， 将进行与目标1和2类似的实验，但在整个肌腱中， 在适应性负荷下，最多可持续5天。连接蛋白43是一种机械连接蛋白， 负荷敏感基因了解肌腱细胞如何生长并对 机械载荷和伤口信号将影响我们对 患者对受伤后的运动疗法有反应。关于运动如何作用的知识 该机制水平可导致用于上调细胞药物策略 老年人或残疾人有或无运动的分割和矩阵表达 患者

DESCRIPTION (Adapted from the Applicant's Abstract): Intercellular communication is essential for homeostatic function of most organs, to coordinate events during development, and to pace contractions in the heart, lungs, gut, erectile tissue and uterus. Published reports from the principal investigator's group now indicate that coordination of cellular activities through gap junctions is vital in flexor tendons in response to mechanical load and wounding. Exercise is critical to health maintenance: normal activity is positive, immobilization is negative and overactivity is destructive. In medicine, motion therapy post-injury is essential to recover range of motion. The applicants hypothesize that coordination of cellular activities through gap junctions is vital in response to mechanical load and after tendon injury. If gap junctions are blocked, cell coordination will be prevented. In Specific Aim 1, they will test the importance of gap junctions in signaling via Ca2+, gap junction translocation with a GFP-cx43 construct, and DNA and collagen synthesis in cells that have been mechanically loaded and wounded in vitro +/- gap junction blockage. Loading will include both acute and adaptive regimens. In Specific Aim 2, they will test the effect of PKC modulation on gap junction expression and function with compounds, such as ATP and norepinephrine, which regulate gap junction signaling and expression. In Specific Aims 3 and 4, they will conduct similar experiments to those in Aims 1 and 2, but in whole tendon, in response to adaptive loading for up to 5 days. Connexin 43 is a mechanical load-sensitive gene. Knowledge of how tendon cells transduce and respond to mechanical load and wound signals will have impact on our understanding of how patients respond to motion therapy post-injury. Knowledge of how motion acts at the mechanistic level may lead to drug strategies for upregulating cell division and matrix expression with or without motion in aged or disabled patients.