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

基本信息

批准号：
7676746
负责人：
Yi-Xian Qin
金额：
$ 32.41万
依托单位：
STATE UNIVERSITY NEW YORK STONY BROOK
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-08-01 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7676746
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 Contralateral 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 Rattus Research Personnel Rest Role Series Shapes Signal Transduction Skeletal Muscle Stimulus Surface Suspension substance Suspensions Testing Tissues Transmission Electron Microscopy Treatment Protocols Vascular blood supply Venous Work base bone bone loss bone turnover capillary cell growth density design fluid flow improved in vivo Model muscle strength osteogenic pressure prevent research study response restoration shear stress skeletal skeletal tissue voltage wasting

项目摘要

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提供营养，氧气和生理流动，并从肌肉和骨骼中移动废物。肌肉骨骼并发症是由于在损伤和功能性残留期间的微循环降低（例如床上和微重力）引起的，对肌肉萎缩和骨质骨质减少症具有显着的生理作用。诸如肌肉收缩之类的运动似乎会增加流向骨骼组织的血液流动，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性适应的关键介体。使用振荡性加压骨髓流动刺激，发现生理液体刺激会引发新的骨形成，并减少因废除而引起的皮质内骨孔，即使在没有直接组织应变的情况下也是如此。虽然骨骼重塑被证明对高动态生理刺激率很敏感，但骨流动在骨和肌肉中的作用可能至少部分解释了对合成代谢刺激的细胞反应机制。在提出的工作中，我们将研究以下一般假设：在动态功能刺激下介导的骨骼肌肉循环充当动态肌肉泵和骨流体流动的关键介体，可控制和促进成骨和肌肉适应。实际上，提高我们的理解肌肉动力学（例如肌肉收缩的频率和幅度），循环和流体流通骨的作用可能有助于设计基于生物力学的干预措施，以治疗骨质疏松症，肌肉萎缩，并加速骨折愈合或促进骨质的骨质愈合或促进骨bono骨。在此应用中，目标将通过一系列亚螺丝和特定目的来实现：（1）动态间质流体流动可以通过骨骼肌功能收缩来启动和增强。功能性肌肉收缩是产生髓内压力并调节静脉回流的动态泵，从而启动骨骼中的流体流动。（2）通过肌肉动力刺激诱导的骨流体流动可以引发表面自适应反应并抑制骨骼内骨骼内骨质的损失。自适应响应将对负载模式的速度敏感。（3）肌肉泵诱导的对合成代谢流体流动刺激的成骨反应取决于产生的流体压力幅度和负载持续时间。（4）肌肉刺激的动态模式的潜力可以引发肌肉适应，其中在生理水平上诱导的负荷将增加毛细血管密度并大大增加肌肉的血液流动，而过载会导致部分肌肉血管性萎缩，而骨血血流后骨骼血流局部疾病。（5）可以通过在动态载荷过程中插入REST preiod来优化肌肉和骨骼中的液体浸润，从而减少液体饱和并改善灌注。（6）在每天但短的持续时间（例如，<10天）的负载持续时间（例如<10天）之后，骨内膜细胞的成骨细胞激活开始，对流体流动刺激的反骨气电位反应。细胞区域，核面积，细胞数，细胞和核形状的组织分析将检查细胞和核的超微结构成骨细胞特征，其中将鉴定出相关的液体成分。