Spatial correlation of osteocyte gene response to local mechanical strain in bone tissue

骨细胞基因对骨组织局部机械应变反应的空间相关性

• 批准号: 9978307
• 负责人: GLEN L NIEBUR
• 金额: $ 18.57万
• 依托单位: UNIVERSITY OF NOTRE DAME
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9978307
• 关键词: Affect; Animal Model; Architecture; Biological; Biology; Bioreactors; Bone Diseases; Bone Matrix; Bone Surface; Bone Tissue; Bone remodeling; Cells; Clinical Data; Complex; Computer Models; Diagnosis; Elements; Environment; Extracellular Matrix; Future; Gene Combinations; Gene Expression; Genes; Goals; Hip Fractures; Human; In Situ Hybridization; Incidence; Individual; Injury; Label; Marrow; Measurement; Measures; Mechanics; Medical Care Costs; Modeling; Morbidity - disease rate; Myocardial Infarction; Nature; Osteoblasts; Osteoclasts; Osteocytes; Osteogenesis; Osteoporosis; Patients; Physiology; Porosity; Prevention; Probability; Proteins; RNA; Research; Research Project Grants; Sensory; Signal Transduction; Signaling Molecule; Skeleton; Specimen; Stress; Stretching; Stroke; System; Testing; Time; Tissue-Specific Gene Expression; Tissues; Weight-Bearing state; base; bone; bone cell; differential expression; experimental study; fluid flow; insight; malignant breast neoplasm; mechanical load; mortality; organizational structure; osteoporosis with pathological fracture; predicting response; protein expression; repaired; response; shear stress; stem cells; substantia spongiosa; transcriptome sequencing

Project Summary There were more than 2 million osteoporotic fractures in the U.S. in 2005, which exceeded the incidence of heart attack, stroke, and breast cancer combined. Osteoporotic fractures are associated with a high level of mortality and morbidity; more than one in five patients who suffer a hip fracture will die within one year due to causes related to their injury. The annual medical costs exceeded $17 billion in 2005 and are expected to increase to $25 billion by 2025. Bone physiology and adaptation are regulated by mechanical loading, which alters gene and protein expression in bone cells. Mechanical loads on bone are sensed by osteocytes embedded in the bone that signal to progenitor cells on the bone surface and in the marrow. Experiments have identified threshold levels of bone strain and cell shear stress that trigger osteocyte signaling, but are generally aggregated over many cells or larger regions of bone. These measures provide limited information about the stochastic or variable nature of cell responses to load. In the near future, computational power will allow models of bone adaptation incorporating response to individual cell signaling molecules to be employed to explore bone physiology and predict the response of bone to new treatments. Such models will provide better insight into experimental and clinical data related to bone diseases. In anticipation of these models, the goal of this project is to measure the probability of expression of key signaling genes in osteocytes based on the local mechanical environment. The aims are to measure gene expression in bone subsequent to controlled loading in a bioreactor system, calculate the stress field using high-fidelity computational models, and perform spatial correlations to determine the likelihood of altered gene expression for a given mechanical environment.

项目摘要 2005年，美国有超过200万例腰椎骨折，超过了2005年的发病率。 心脏病中风和乳腺癌骨质疏松性骨折与高水平的 死亡率和发病率;超过五分之一的髋部骨折患者将在一年内死亡， 与其受伤有关的原因。2005年，每年的医疗费用超过170亿美元，预计 到2025年增加到250亿美元。 骨生理和适应性受机械负荷调节，机械负荷改变基因和蛋白质 在骨细胞中的表达。骨上的机械负荷由嵌入骨中的骨细胞感知， 向骨表面和骨髓中的祖细胞发出信号。实验表明， 骨应变和细胞剪切应力，触发骨细胞信号，但通常聚集在许多 细胞或更大的骨区域。这些措施提供了有限的信息有关的随机或变量 细胞对负荷的反应性质。 在不久的将来，计算能力将允许骨骼适应模型结合对 单个细胞信号分子用于探索骨生理学和预测 新的治疗方法。这些模型将更好地了解与以下相关的实验和临床数据： 骨疾病在这些模型的预期中，本项目的目标是测量 基于局部机械环境的骨细胞中关键信号基因的表达。其宗旨是 测量生物反应器系统中受控加载后骨中的基因表达，计算应力 场使用高保真计算模型，并执行空间相关性，以确定的可能性 在给定的机械环境下改变基因表达。