EFFECTS OF MECHANICAL STRAIN ON OSTEOCYTE FUNCTION

机械应变对骨细胞功能的影响

• 批准号: 6488197
• 负责人: Lynda F Bonewald
• 金额: $ 66.84万
• 依托单位: UNIVERSITY OF MISSOURI KANSAS CITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6488197
• 关键词: cytology; mechanical stress; osteocytes

Significance: Although osteocytes make up over 90% of all bone cells, little is known about their function, compared to other bone cells, the osteoblast and the osteoclast. The osteocyte is the cell ideally situated in bone to sense mechanical strain and translate that strain into signals for bone formation and bone resorption. However, the role of osteocytes in modulating strain effects on bone modeling and remodeling is unclear: Approach: This Program Project Application was initiated to develop a time approach to clarify the mechanisms by which osteocytes sense and respond to mechanical strain in a manner that results in either bone loss, remodeling, or pathologic repair. The focus of this application is to determine the role of the osteocyte in signaling bone resorption. The mechanisms whereby osteocytes translate mechanical strain into signals include intracellular and extracellular signaling initiate or controlling osteoblast/osteoclast activity and the expression of genes necessary and specific for osteocyte function. The specific aims of the program project are: 1) determine the role and regulation of gap junction function in osteocytes, 2) to determine the levels of mechanical strains sensed by the osteocyte resulting from the mechanical stimulation of bone, 3) to identify osteocyte specific genes and their regulation by mechanical strain and 4) to determine the role of the osteocyte in osteoclast formation. Innovation: Novel approaches to answer these questions include the use of an osteocyte-like cell line, the use of bioengineering micro- mechanisms techniques to measure strain sensed by individual osteocytes, fluorescence image analysis to examine gene expression in single cells, novel animal models, and gene array technology to examine genes regulated by mechanical strain. Investigators and Environment: The program project is composed of investigators with specific talents, training and expertise in the areas of molecular biology, cell known for its contributions in the area of bone and cartilage biology. Knowledge gained will lead to identification of ways to regulate or inhibit the osteocytic signals of resorption that can be used towards the prevention and treatment of bone loss due to immobilization, space flight, microdamage, aging and disease states such as osteoporosis.

重要性：虽然骨细胞占所有骨细胞的90%以上，但与其他骨细胞（成骨细胞和破骨细胞）相比，对其功能知之甚少。骨细胞是理想地位于骨中以感知机械应变并将该应变转化为骨形成和骨吸收的信号的细胞。然而，骨细胞在调节应变对骨建模和重塑的影响中的作用尚不清楚：方法：本计划项目申请旨在开发一种时间方法，以阐明骨细胞感知和响应机械应变的机制，从而导致骨丢失，重塑或病理修复。本申请的重点是确定骨细胞在骨吸收信号传导中的作用。骨细胞将机械应变转化为信号的机制包括细胞内和细胞外信号传导启动或控制成骨细胞/破骨细胞活性以及骨细胞功能所必需和特异性基因的表达。该计划项目的具体目标是：1）确定骨细胞间隙连接功能的作用和调节，2）确定骨细胞因骨的机械刺激而感受到的机械应变水平，3）确定骨细胞特异性基因及其通过机械应变的调节，以及4）确定骨细胞在破骨细胞形成中的作用。创新：回答这些问题的新方法包括使用骨细胞样细胞系、使用生物工程微机制技术来测量单个骨细胞所感知的应变、荧光图像分析来检查单细胞中的基因表达、新的动物模型和基因阵列技术来检查受机械应变调节的基因。研究者和环境：该计划项目由具有特定人才，分子生物学领域的培训和专业知识的研究人员组成，细胞以其在骨和软骨生物学领域的贡献而闻名。所获得的知识将导致确定调节或抑制骨细胞再吸收信号的方法，这些方法可用于预防和治疗由于固定、空间飞行、微损伤、衰老和骨质疏松症等疾病引起的骨丢失。