Connective Tissue Mechanotransduction

结缔组织机械传导

• 批准号: 7795980
• 负责人: HELENE M LANGEVIN
• 金额: $ 37.25万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7795980
• 关键词: Absenteeism; Actomyosin; Acupuncture procedure; Acute; Alternative Therapies; Architecture; Articular Range of Motion; Behavior; Biomechanics; Cell Differentiation process; Cells; Cellular biology; Characteristics; Chronic; Collagen; Connective Tissue; Cytoskeletal Modeling; Dose; Fibroblasts; Foundations; Functional disorder; Gene Expression; Gene Proteins; Genes; Goals; Grant; Health; Hour; Injury; Investigation; Knowledge; Lead; Length; Link; Loose connective tissue; Maintenance; Manuals; Mechanical Stimulation; Mechanics; Mediating; Modeling; Movement; Mus; Muscle; Musculoskeletal; Musculoskeletal Pain; Needles; Nuclear; Pain; Pattern; Physical therapy; Physiological; Physiology; Play; Posture; Prevention; Property; Proteins; Reaction Time; Regulation; Research; Rest; Role; Rotation; Side; Signal Transduction; Skeletal Muscle; Solid; Source; Sports Medicine; Stimulus; Stretching; System; Testing; Therapeutic; Time; Tissue Sample; Tissues; Up-Regulation; Work; base; cost; disability; improved; in vivo; inhibitor/antagonist; injury prevention; insight; mouse model; novel; prevent; protein expression; public health relevance; research study; response; soft tissue

DESCRIPTION (provided by applicant): An important goal of physical therapy, sports medicine and many complementary and alternative (CAM) therapies is the prevention of injuries through promotion and maintenance of optimal musculoskeletal function. A wide variety of treatments including manual and movement-based therapies are concerned with optimizing body alignment, posture, biomechanics and quality of movement. Many of these treatments involve stretching of soft tissues within or slightly beyond their usual range of motion, either manually or actively. Despite this widespread use, the effect of tissue stretch is poorly understood, with the majority of research so far being on muscle, with comparatively little on connective tissue. In our previous grant, we demonstrated a novel, dynamic response of connective tissue fibroblasts to tissue stretch. Static stretching of "loose" inter-fascial connective tissue causes extensive fibroblast cytoskeletal remodeling within 10 minutes, followed within 90 minutes by up-regulation of a large group of skeletal muscle- related genes. We also found that similar effects occur with acupuncture needle rotation due to winding and gathering of collagen around the rotating needle, essentially stretching the tissue "from the inside". A potentially important difference between acupuncture and tissue stretch, however, is that a "whorl" of collagen formed during needle rotation can persist after the needle has been withdrawn, thus causing a more prolonged stretching of tissue compared with simple stretch followed by release. In this project Renewal, we propose to expand our investigation of this active fibroblast response to tissue stretch, with the goals of characterizing its time course and dose-response characteristics (Aim 1), mechanotransduction mechanisms linking cytoskeletal and nuclear remodeling to intracellular signaling and gene expression (Aim 2) as well as downstream effects on fibroblast muscle-related protein expression and connective tissue tension regulation (Aim 3). We will use ex vivo and in vivo mouse models developed in our previous grant. Our results will be relevant to basic cell biology, connective tissue physiology, manual and movement based therapies as well as acupuncture. We believe that understanding this new phenomenon will lead to fundamental insights into the role played by mechanical stimulation in maintaining healthy connective tissue function. This expanded knowledge of normal physiology will potentially lead to discovering types of connective tissue dysfunction that are not currently recognized. An improved understanding of connective tissue physiology and pathophysiology will therefore provide a fundamentally broader and more solid foundation for understanding the therapeutic mechanisms of a wide range of conventional and alternative therapies and practices aimed at improving wellness, preventing injuries and treating musculoskeketal pain. PUBLIC HEALTH RELEVANCE. Chronic musculoskeletal pain resulting from acute or repetitive injuries is a major source of disability, work absenteeism and health case costs. In addition to treating pain, an important goal of physical therapy, sports medicine and many complementary and alternative (CAM) therapies is the prevention of injuries through promotion and maintenance of optimal musculoskeletal function. This project will investigate a novel response of connective tissue to mechanical stimulation, initially described in our previous grant, that will broaden the foundation for an expanded understanding of musculoskeletal wellness, prevention and treatment.

描述（由申请人提供）：物理治疗、运动医学和许多补充和替代（CAM）疗法的一个重要目标是通过促进和维持最佳的肌肉骨骼功能来预防损伤。包括手法和运动疗法在内的多种治疗方法都涉及优化身体排列、姿势、生物力学和运动质量。许多这些治疗涉及手动或主动地在其通常的运动范围内或稍微超出其通常的运动范围拉伸软组织。尽管用途广泛，但人们对组织拉伸的影响知之甚少，迄今为止，大多数研究都针对肌肉，而针对结缔组织的研究相对较少。在我们之前的资助中，我们展示了结缔组织成纤维细胞对组织拉伸的新颖的动态反应。 “松散的”筋膜间结缔组织的静态拉伸在 10 分钟内引起广泛的成纤维细胞骨架重塑，随后在 90 分钟内上调一大群骨骼肌相关基因。我们还发现，由于胶原蛋白围绕旋转针缠绕和聚集，针灸针旋转也会产生类似的效果，本质上是“从内部”拉伸组织。然而，针灸和组织拉伸之间的一个潜在的重要区别是，在针旋转过程中形成的胶原蛋白“螺纹”在针退出后仍会持续存在，从而与简单拉伸然后释放相比，导致组织拉伸时间更长。在这个 Renewal 项目中，我们建议扩大对这种对组织拉伸的活跃成纤维细胞反应的研究，目标是表征其时间过程和剂量反应特征（目标 1）、将细胞骨架和核重塑与细胞内信号传导和基因联系起来的机械转导机制表达（目标 2）以及对成纤维细胞肌肉相关蛋白表达和结缔组织张力调节（目标 3）的下游影响。我们将使用我们之前资助中开发的离体和体内小鼠模型。我们的结果将与基础细胞生物学、结缔组织生理学、手法和运动疗法以及针灸相关。我们相信，了解这一新现象将有助于深入了解机械刺激在维持健康结缔组织功能中所起的作用。对正常生理学知识的扩展将有可能发现目前尚未认识到的结缔组织功能障碍类型。因此，对结缔组织生理学和病理生理学的进一步了解将为理解旨在改善健康、预防损伤和治疗肌肉骨骼疼痛的各种常规和替代疗法和实践的治疗机制提供更广泛和更坚实的基础。公共卫生相关性。 急性或重复性损伤引起的慢性肌肉骨骼疼痛是残疾、缺勤和医疗费用的主要原因。除了治疗疼痛之外，物理治疗、运动医学和许多补充和替代 (CAM) 疗法的一个重要目标是通过促进和维持最佳的肌肉骨骼功能来预防损伤。该项目将研究结缔组织对机械刺激的新反应，最初在我们之前的资助中进行了描述，这将为扩大对肌肉骨骼健康、预防和治疗的理解奠定基础。