TENDON CELLS:INTERACTIONS & RESPONSES TO STRESS IN VITRO

肌腱细胞：相互作用

• 批准号: 6511683
• 负责人: ALBERT J BANES
• 金额: $ 21.74万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-08-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6511683
• 关键词: Aves; biological signal transduction; calcium flux; cell cell interaction; collagen; fibroblasts; gap junctions; green fluorescent proteins; growth factor; mechanical stress; membrane channels; mixed tissue /cell culture; phosphorylation; protein biosynthesis; protein kinase C; proteoglycan; tendon injury; wound healing

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.

描述（改编自申请人的摘要）：细胞间 沟通对于大多数器官的稳态功能至关重要， 在开发过程中协调事件，并为心脏加快收缩， 肺，肠道，勃起组织和子宫。校长的发布报告 现在，研究者的小组表明细胞活动的协调 通过间隙连接在机械载荷的响应中至关重要 和受伤。运动对健康维护至关重要：正常活动是 积极，固定是负面的，过度活动是破坏性的。在 医学，运动疗法伤害后对于恢复运动范围至关重要。 申请人假设通过间隙协调细胞活动 连接对机械负荷和肌腱损伤后至关重要。如果 缝隙连接被阻塞，将防止细胞配位。在特定目标中 1，他们将测试差距连接在通过CA2+的信号传导中的重要性 与GFP-CX43结构以及DNA和胶原蛋白的交界处易位 在体外已机械加载和受伤的细胞中的合成+/- 间隙连接阻塞。负载将包括急性和适应性方案。 在特定目标2中，他们将测试PKC调制对间隙连接的影响 具有化合物的表达和功能，例如ATP和去甲肾上腺素，它们 调节间隙连接信号传导和表达。在特定的目标3和4中，他们 将进行与目标1和2中的实验相似的实验，但在整个肌腱中， 响应自适应加载长达5天。连接蛋白43是机械 负载敏感基因。了解肌腱细胞如何转导和响应 机械负荷和伤口信号将影响我们对如何的理解 患者对伤害后的运动疗法做出反应。了解运动如何在 机械水平可能导致上调细胞的药物策略 在老年或残疾人的情况下，有或没有运动的分裂和矩阵表达 患者。