TENDON CELLS--INTERACTIONS AND RESPONSES TO STRESS

肌腱细胞——相互作用和对压力的反应

• 批准号: 3158416
• 负责人: ALBERT J BANES
• 金额: $ 9.83万
• 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 1990-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3158416
• 关键词: cell cell interaction; cell cycle; cell growth regulation; chickens; collagen; crosslink; exercise; fibroblasts; fluorescence microscopy; immobilization of body part; mechanical stress; protein biosynthesis; synovial fluid; tendon injury; tendons; tissue /cell culture; vascular endothelium; wound healing

Tendon injuries, particularly sports-related injuries, constitute an increasing proportion of cases treated at our hospital, yet research in the molecular and cell biology of tendon healing is in its embryonic stages. Morphological, biomechanical and biochemical studies of normal tendon have revealed fundamental architecture, that exercise enhances healing and that fewer collagen crosslinks can be correlated with increased range of motion during convalescence after tendon injury. The overall objective of this study is to establish, on the molecular level, how exercise alters the metabolism of tendon cells to yield the proper balance between cell division and matrix production resulting in a healed tendon that is strong yet flexible. Results of recent experiments in this laboratory indicate that aortic endothelial cells respond to a repeating stress cycle of 10 sec 10% elongation and 10 sec relaxation in vitro by increasing their rate of division. The same stress regimen decreases the division rate of tendon fibroblasts. These different responses to the same stress field seem reasonable given that endothelial cells need to completely cover the interior of a blood vessel and regulate transport, but do not contribute much mechanical strength, whereas an organ such as tendon requires great tensile strength to transmit the force of muscle contraction to bone effect limb movement. In this case, if tendon became highly cellular, it would have insufficient mechanical strength to perform its work. Hence cyclic stress to tendon probably results in matrix production and not cell division. The important conclusion is that the response to physical stress probably varies for each tissue and may depend on the nature of the stress as well as the cell type affected. It should be possible to define what regimen activates a given cell to produce one of two principle effects: an alteration in cell division or matrix production. It is most likely that rapid changes in cells, occurring in secs or mins, could be involved in signal reception or transduction related to the magnitude of the stress. Slower responses involved in long term reactions would involve whether or not cells divide or produce matrix resulting in tissue build-up or degradation affecting the ultimate strength and flexibility of the tissue. In this proposal, I intend to correlate cell metabolism and matrix qualities of living tendon subjected to exercise or immobilization, the two extremes of applied force in vivo with those of cells subjected to applied force in vitro.

肌腱损伤，特别是与运动相关的损伤，构成了 在我们医院接受治疗的病例比例不断增加，但 肌腱愈合的分子和细胞生物学研究正在进行 它的萌芽阶段。 形态学、生物力学和 对正常肌腱的生化研究揭示了基本原理 建筑，运动可以增强愈合，并且更少 胶原交联可以与范围的增加相关 肌腱损伤后恢复期的运动。 整体 本研究的目的是在分子水平上确定如何 运动改变肌腱细胞的新陈代谢，以产生适当的 细胞分裂和基质产生之间的平衡导致 愈合后的肌腱坚固而柔韧。 最近的结果 本实验室的实验表明，主动脉内皮细胞 细胞对 10 秒 10% 伸长的重复应力循环做出反应 以及通过增加分裂速率在体外松弛 10 秒。 相同的应力方案会降低肌腱的分裂率 成纤维细胞。 对相同应力场的这些不同反应 鉴于内皮细胞需要完全 覆盖血管内部并调节运输，但确实 不会贡献太多的机械强度，而这样的器官 因为肌腱需要很大的抗拉强度来传递力量 肌肉收缩使骨骼影响肢体运动。 在这种情况下，如果 肌腱变得高度细胞化，它就没有足够的 执行其工作的机械强度。 因此循环应力 肌腱可能导致基质产生而不是细胞分裂。 重要的结论是对身体压力的反应 每个组织可能有所不同，并且可能取决于组织的性质 压力以及受影响的细胞类型。 应该是可以的 定义什么方案激活给定细胞产生以下之一 两个主要影响：细胞分裂或基质的改变 生产。 细胞的快速变化很可能发生 在几秒或几分钟内，可能涉及信号接收或 与应力大小相关的转导。 慢点 涉及长期反应的反应将涉及是否 或细胞不分裂或产生基质导致组织形成或 退化影响最终强度和柔韧性 组织。 在这个提案中，我打算将细胞代谢与 受到锻炼或活动的活肌腱的基质质量 固定，体内施加力的两个极端 那些在体外受力的细胞。