Does aging decrease osteocyte lacunar-canalicular bone quality?

衰老是否会降低骨细胞腔隙骨质量？

基本信息

批准号：
10377518
负责人：
Chelsea Marie Heveran
金额：
$ 7.2万
依托单位：
MONTANA STATE UNIVERSITY - BOZEMAN
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-01 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10377518
关键词：
3-Dimensional Accounting Affect Age Aging Apoptotic Atomic Force Microscopy Behavior Bone Resorption Bone Tissue Bone remodeling C57BL/6 Mouse Calcium Characteristics Collagen Contralateral Data Deposition Disease Elderly Electron Microscopy Electrons Evaluation Female Femur Fluorochrome Fracture Geometry Goals Health Care Costs High Resolution Computed Tomography Histology Human Image Immunohistochemistry Injury Knowledge Label Laser Scanning Confocal Microscopy Liquid substance Longevity Maintenance Maps Measures Mediating Methods Minerals Modulus Morphology Mus Nitrogen Osteocytes Pharmaceutical Preparations Physiological Play Raman Spectrum Analysis Research Resistance Resolution Role Rosaniline Dyes Shapes Spectrum Analysis Stains System Testing Therapeutic Therapeutic Intervention Tissues United States Variant Work age related aged bone bone cell bone fragility bone loss bone quality effectiveness evaluation exercise intervention human old age (65+)improved innovation insight male middle age nano older patient senescence skeletal submicron therapeutic target tool young adult

项目摘要

Project Summary Bone fracture is common in aging, yet therapies for maintaining bone quality in aging are limited. The osteocyte participates in bone quality maintenance and may be a promising therapeutic target for bone fragility in aging. Osteocytes reside within bone in lacunae that are connected by canaliculi. The osteocyte can both resorb and deposit bone tissue adjacent to the immense lacunar-canalicular system (LCS). Aging diminishes the number and size of lacunae and canaliculi and also changes several aspects of osteocyte behavior. However, these changes in lacunar and canalicular morphologies do not reveal how the fraction of osteocytes engaged in bone resorption or deposition change in aging. Likewise, changes to the amount of remodeled bone near lacunae and canaliculi due to aging are not known. Thus, there are critical gaps in the understanding of how aging impacts osteocyte-mediated bone quality. The overarching hypothesis of this work is that LCS remodeling increases bone quality by decreasing bone mineral and matrix maturity near osteocytes, and that with increased age, less osteocytes participate in LCS remodeling. One Aim is proposed to investigate this hypothesis. Femurs from skeletally-mature young adult (6 mo), middle-age (18 mo), and aged (24 mo) female and male C57Bl/6 mice will be studied for lacunar-canalicular remodeling characteristics. The fraction of osteocytes participating in bone mineral and matrix resorption will be evaluated from histology and immunohistochemistry, while the fraction of bone-forming osteocytes will be assessed by measuring lacunae positive for fluorochrome labels. For each age, mineral and matrix will be mapped for bone-forming and non-bone-forming osteocyte lacunae using Auger Electron Spectroscopy (AES) at submicron resolution. Complementary submicroscale-resolution Atomic Force Microscopy (AFM) maps of the same lacunae will identify the impact of osteocyte remodeling on bone tissue modulus. AES and AFM maps will also be generated for canaliculi. Osteocyte lacunar and canalicular morphologies will be measured for the same femurs. Completion of this project will significantly advance the understanding of how osteocytes remodel bone across the lifespan. The project will also answer the question of whether changes to osteocyte lacunar and canalicular geometries in aging is associated with loss of bone quality near the osteocyte. The innovative use of Auger Electron Spectroscopy and complementary Atomic Force Microscopy will provide new insights into how aging changes bone quality at physiologically-relevant resolution adjacent to the lacunar-canalicular system. This approach is expected to have broad utility for evaluating the impacts of disease, injury, and therapeutics on osteocyte-mediated bone quality. The long-term goal of this research is to investigate whether osteocyte behavior can be changed through therapeutic interventions to influence LCS remodeling and improve skeletal fracture resistance.

项目摘要骨折在衰老中很常见，但是维持衰老骨质质量的疗法受到限制。这骨细胞参与骨质质量维持，可能是骨脆弱的有前途的治疗靶标在衰老中。骨细胞居住在骨的骨骼内，这些骨细胞与Canaliculi相连。骨细胞都可以吸收和沉积与巨大的lacunar-cansicular系统（LCS）相邻的骨组织。老化减少空隙和河囊的数量和大小，也改变了骨细胞行为的几个方面。但是，lacunar和口腔形态的这些变化并未揭示骨细胞的分数从事骨骼吸收或沉积变化。同样，更改已重塑的量由于衰老而导致的空隙和管子附近的骨头尚不清楚。因此，在了解衰老如何影响骨细胞介导的骨质质量。这项工作的总体假设是否通过降低骨矿物质和基质成熟度来提高骨骼质量骨细胞，随着年龄的增长，骨细胞较少参与LCS重塑。提出了一个目标研究这一假设。来自骨骼成熟的年轻成人（6个月），中年（18个月）的股骨，将研究年龄（24个月）的雌性和雄性C57BL/6小鼠，以实现lacunar-cansilicular重塑特性。参与骨矿物质和基质吸收的骨细胞的比例将从组织学评估和免疫组织化学，而骨形成骨细胞的比例将通过测量来评估荧光素标签的空隙阳性。对于每个年龄，矿物和基质将被映射以进行骨形成在亚微米分辨率下，使用螺旋钻电子光谱（AES）和非骨形成骨细胞空隙。互补的亚显微镜分辨率原子力显微镜（AFM）图将确定骨细胞重塑对骨组织模量的影响。 AES和AFM地图也将是为canaliculi生成。骨细胞lacunar和管道形态将用于相同股骨。该项目的完成将大大提高对骨细胞的重塑骨的理解整个生命周期。该项目还将回答一个问题，即是否会更改骨细胞lacunar和衰老中的管道几何形状与骨细胞附近的骨骼质量丧失有关。创新的用途螺旋钻电子光谱和互补原子力显微镜将提供新的见解衰老如何在与lacunar-canalicular相邻的生理上尚不相关的分辨率上改变骨质质量系统。预计这种方法将具有广泛的效用，以评估疾病，伤害和骨细胞介导的骨质质量的治疗剂。这项研究的长期目标是调查是否可以通过治疗干预措施改变骨细胞行为，以影响LCS重塑和提高骨骼骨折抗性。