TENDON CELLS:INTERACTIONS & RESPONSES TO STRESS IN VITRO

肌腱细胞：相互作用

• 批准号: 6632519
• 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/6632519
• 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 协调发育过程中的事件，并调节心脏收缩的速度， 肺、肠道、勃起组织和子宫。校长发表的报告 研究小组现在表明细胞活动的协调 通过间隙连接对于屈肌腱响应机械负载至关重要 和伤人。锻炼对于维持健康至关重要：正常活动是 积极的是，固定是消极的，过度活动是破坏性的。在 医学上，受伤后的运动治疗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 连接对于机械负荷和肌腱损伤后的反应至关重要。如果 间隙连接被阻断，细胞协调就会受到阻碍。特定目标 1，他们将测试间隙连接在 Ca2+、间隙信号传导中的重要性 与 GFP-cx43 构建体以及 DNA 和胶原蛋白的连接易位 在体外受到机械负载和损伤的细胞中合成 +/- 间隙连接堵塞。负荷将包括急性和适应性治疗方案。 在具体目标 2 中，他们将测试 PKC 调节对间隙连接的影响 ATP 和去甲肾上腺素等化合物的表达和功能， 调节间隙连接信号传导和表达。在具体目标 3 和 4 中，他们 将进行与目标 1 和 2 中类似的实验，但在整个肌腱中， 响应自适应加载长达 5 天。 Connexin 43 是一种机械 负荷敏感基因。了解肌腱细胞如何转导和响应 机械负载和伤口信号将影响我们对如何进行理解 患者对受伤后的运动疗法有反应。了解运动如何作用于 机制水平可能导致上调细胞的药物策略 老年人或残疾人有或没有运动的除法和矩阵表达 患者。