Effect of Aging on the Osteocyte Lacuna Microenvironment

衰老对骨细胞腔隙微环境的影响

基本信息

批准号：
7457903
负责人：
DANIEL P NICOLELLA
金额：
$ 21.23万
依托单位：
SOUTHWEST RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-07-01 至 2010-06-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): This is an exploratory proposal aimed at characterizing the microenvironment of bone tissue around osteocyte lacunae (herein referred to as peri-lacunar tissue) as a function of age. Comprising nearly 90% of all bone cells, osteocytes are ideally situated to sense mechanical strain (or a lack of strain) and translate mechanical signals into biochemical signals to regulate bone modeling and remodeling. We have shown that there is an amplification of globally applied macroscopic bone strains at the microstructural level of the osteocyte due to the strain concentrating effect of the osteocyte lacuna and surrounding extracellular matrix. Our preliminary data indicates that the peri-lacunar bone tissue can have different material and mechanical properties than bone tissue not associated with an osteocyte lacuna and that these alterations can result in significant changes in prei-lacunar tissue strain. Our global hypothesis is that the aging extracellular matrix (ECM) attenuates the strain signals sensed by osteocytes. Specifically, we hypothesize that the local peri-lacunar strain decreases as a function of increasing age at given macroscopic, whole bone strain levels and that this decrease in peri-lacunar tissue strain is a result of age-related increases in mineral-to-collagen ratio and declines in collagen integrity in the peri-lacunar tissue. To test this hypothesis, we propose to examine if ultrastructural properties near the lacunae change with age and if such changes are associated with a decrease in strain concentration around lacunae. We propose the following specific aims: Specific Aim 1: We will measure osteocyte peri-lacunar tissue deformation in human cortical bone from donors of varying age. We hypothesize that for the same macroscopic bone strain, the local peri-lacunar tissue strain will decrease as a function of donor age. Specific Aim 2: We will characterize the material properties of the extracellular matrix surrounding osteocytes in cortical bone from donors of varying age. We hypothesize that the mineral-to-collagen ratio, stiffness, and stable cross-links will be higher in older bone than in younger bone. The findings from the proposed research project will offer new insights in bone mechanotransduction and a better understanding of age-related declines in bone strength. This new understanding may lead to improved treatment for bone diseases such as osteoporosis.

描述（由申请人提供）：这是一项探索性建议，旨在将骨组织周围的骨组织微环境（以下称为lacunar骨组织）作为年龄的函数。骨细胞占所有骨细胞的近90％，理想地位于感知机械应变（或缺乏应变），并将机械信号转化为生化信号，以调节骨建模和重塑。我们已经表明，由于骨细胞间隙和周围细胞外基质的应变浓度效应，在整骨细胞的微结构水平上进行了全球施加的宏观骨骼菌株的扩增。我们的初步数据表明，与与骨细胞无关的骨骼组织相比，乳牙周围的骨骼组织可能具有不同的材料和机械性能，并且这些改变会导致前乳清组织菌株的显着变化。我们的全球假设是，衰老的细胞外基质（ECM）减弱了骨细胞感受的应变信号。具体而言，我们假设，在给定的宏观，整个骨骼应变水平上，局部螺旋杆菌株的降低是年龄增加的函数，并且这种降低是由于年龄相关的矿物质与胶原蛋白比的增加，而矿物质与胶原蛋白比的增加，并且在周围的乳牙组织中胶原蛋白的整合性下降。为了检验这一假设，我们建议检查空白附近的超微结构特性是否随着年龄的增长而变化，以及这种变化是否与lacunae周围的应变浓度降低有关。我们提出以下特定目的：具体目标1：我们将通过不同年龄的供体来测量人皮质骨的骨细胞乳清周围组织变形。我们假设对于相同的宏观骨骼应变，局部lacunar组织应变将随着供体年龄的函数而降低。具体目标2：我们将表征来自不同年龄的供体的皮质骨中骨细胞周围骨细胞周围骨细胞的材料特性。我们假设矿物与胶原蛋白的比例，刚度和稳定的交联在老年骨骼中的比率将高于年轻的骨骼。拟议的研究项目的发现将提供有关骨骼机械转导的新见解，并更好地了解与年龄相关的骨骼强度下降。这种新的理解可能会改善骨质疏松症等骨骼疾病的治疗。