Role of Musculo-Dynamics in Bone Fluid Flow, Circulation and Adaptation

肌肉动力学在骨液流动、循环和适应中的作用

• 批准号: 7274884
• 负责人: Yi-Xian Qin
• 金额: $ 33.07万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7274884
• 关键词: Animals; Area; Arteries; Atrophic; Bed rest; Blood Circulation; Blood capillaries; Blood flow; Bone Formation Inhibition; Bone Surface; Bone remodeling; Cell Count; Cell Line; Cell Nucleus; Cells; Condition; Contralateral; Daily; Devices; Exercise; Femur; Filtration; Fracture Healing; Frequencies; Goals; Growth Factor; Histology; Immobilization; Infiltration; Injury; Intercellular Fluid; Intervention; Ischemia; Isometric Exercise; Leg; Limb structure; Liquid substance; Marrow; Measurement; Measures; Mechanics; Mediating; Mediator of activation protein; Microcirculation; Microgravity; Microspheres; Mitochondria; Modeling; Molecular; Monitor; Muscle; Muscle Contraction; Muscular Atrophy; Musculoskeletal; Nuclear; Nutrient; Optics; Osteogenesis; Osteoporosis; Oxygen; Pattern; Perfusion; Physiological; Porosity; Prosthesis; Protocols documentation; Pump; Rate; Rattus; Research Personnel; Rest; Role; Series; Shapes; Signal Transduction; Skeletal Muscle; Skeletal bone; Skeletal system; Stimulus; Surface; Suspension substance; Suspensions; Testing; Tissues; Transmission Electron Microscopy; Treatment Protocols; Vascular blood supply; Venous; Week; Work; base; bone; bone loss; bone turnover; capillary; cell growth; day; density; design; fluid flow; improved; in vivo Model; muscle strength; pressure; prevent; research study; response; restoration; shear stress; voltage; wasting

DESCRIPTION (provided by applicant): Musculoskeletal microvascular circulations supply nutrients, oxygen and physiological flow to and move waste from muscle and bone. Musculoskeletal complications, induced by reduced microcirculation in the condition during injury and functional disuse (e.g., bedrest and microgravity), have significant physiological effects in muscle atrophy and osteopenia. Exercise such as muscle contraction appears to increase blood flow to the skeletal tissues, i.e., bone and muscle. Musculo-dynamics induced bone fluid flow is proposed as a critical mediator in initiating and regulating osteonal adaptation. Using oscillatory pressurized marrow fluid flow stimuli, the physiological fluid stimulus was found to initiate new bone formation and reduce intracortical bone porosities caused by disuse, even in the absence of direct tissue strain. While bone remodeling was demonstrated to be sensitive to high rate of dynamic physiological stimulation, the role of fluid flow in both bone and muscle perhaps explains, at least in part, the cellular response mechanism to anabolic stimuli. In the work proposed, we will examine the general hypothesis that skeletal musculocirculation, mediated at dynamic functional stimulation, serves as a dynamic muscle pump and a critical mediator for bone fluid flow, which controls and promotes osteogenic and muscular adaptation. Indeed, improving our understanding the roles of muscular dynamics (e.g., frequency and magnitude of muscle contraction), circulations, and fluid flow through bone may help to devise a biomechanically based intervention for treating osteoporosis, muscle atrophy, and accelerating fracture healing or promoting bony ingrowth into prostheses. In this application, the goal will be achieved by a series of sub-hypotheses and specific aims: (1) Dynamic interstitial fluid flow can be initiated and enhanced by functional contraction of skeletal muscle. Functional muscle contraction serves as a dynamic pump to generate intramedullary pressure and regulates venous return, which initiate fluid flow in bone. (2) Bone fluid flow induced by musculo-dynamic stimulation can initiate surface adaptive response and inhibit intracortical bone loss in a disuse bone. The adaptive response will be sensitive to the rate of loading patterns. (3) Osteogenic response to anabolic fluid flow stimuli induced by muscle-pump is dependent on generated fluid pressure magnitude and loading duration. (4) The potentials of dynamic patterns of muscle stimuli can initiate muscular adaptation, in which loads induced at the physiological level will increase capillary density and substantially increase blood flow in muscle, while overloading will cause partial musculovascular atrophy following bone bloodflow ischemia. (5) Fluid infiltration in muscle and bone can be optimized by insertion of rest preiod during dynamic loading, which reduce the fluid saturation and improve perfusion. (6) The osteogenic potentials response to fluid flow stimuli is initiated by osteoblastic activation of bone lining cells, following a daily but short duration (e.g., <10 days) of loading. Ultrastructural osteoblastic features of cell and nuclei will be examined via histomorphometric analysis of cell area, nuclear area, cell number, cell and nuclei shapes, in which associated fluid components will be identified.

描述（由申请人提供）：肌肉骨骼微血管循环为肌肉和骨骼提供营养、氧气和生理流量，并从肌肉和骨骼中排出废物。肌肉骨骼并发症，由损伤和功能废用期间的微循环减少引起（例如，卧床休息和微重力）对肌肉萎缩和骨质减少具有显著的生理影响。诸如肌肉收缩的运动似乎增加了流向骨骼组织的血液，即，骨骼和肌肉。肌肉动力学诱导的骨液流动被认为是启动和调节骨适应的关键介质。使用振荡加压骨髓液流刺激，生理流体刺激被发现启动新骨形成和减少皮质内的废用引起的骨孔隙度，即使在没有直接的组织应变。虽然骨重建被证明是敏感的高速率的动态生理刺激，骨和肌肉中的流体流动的作用可能解释，至少部分地，细胞反应机制的合成代谢刺激。在提出的工作中，我们将研究的一般假设，骨骼肌循环，介导的动态功能刺激，作为一个动态的肌肉泵和骨液流动，控制和促进成骨和肌肉适应的关键调解人。事实上，提高我们对肌肉动力学作用的理解（例如，肌肉收缩的频率和幅度）、循环和通过骨的流体流动可以帮助设计用于治疗骨质疏松症、肌肉萎缩和加速骨折愈合或促进骨长入假体的基于生物力学的干预。 在本应用中，将通过一系列子假设和具体目标来实现目标：（1）动态间质液流动可以通过骨骼肌的功能性收缩来启动和增强。功能性肌肉收缩作为动力泵产生髓内压力并调节静脉回流，从而启动骨内液体流动。(2)肌肉动力刺激诱导的骨液流动可以启动表面适应性反应，抑制废用骨皮质内骨丢失。自适应响应将对加载模式的速率敏感。(3)肌泵诱导的合成代谢流体流刺激的成骨反应取决于所产生的流体压力大小和加载持续时间。(4)肌肉刺激的动态模式的潜力可以启动肌肉适应，其中在生理水平上诱导的负荷将增加毛细血管密度并显著增加肌肉中的血流量，而过载将导致骨血流缺血后的部分肌血管萎缩。(5)在动态负荷过程中，通过引入休息时间，可以优化肌肉和骨骼中的液体浸润，从而降低液体饱和度，改善灌注。(6)对流体流动刺激的成骨电位响应是由骨衬里细胞的成骨细胞活化引发的，在每天但短的持续时间（例如，<10天）的装载量。通过对细胞面积、细胞核面积、细胞数量、细胞和细胞核形状进行组织形态计量学分析，检查细胞和细胞核的超微结构成骨细胞特征，其中将识别相关的液体成分。