Analysis of gene expression and cell function in single cell cortical osteoblasts

单细胞皮质成骨细胞的基因表达和细胞功能分析

基本信息

批准号：
8697013
负责人：
Simon Melov
金额：
$ 19.82万
依托单位：
BUCK INSTITUTE FOR RESEARCH ON AGING
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-05 至 2015-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8697013
关键词：
Abdomen Address Adipose tissue Adverse effects Age Age-Related Bone Loss Aging Antibodies Bioenergetics Bone Diseases Cell Line Cell physiology Cells Characteristics Combat Disorders Demography Diabetes Mellitus Disease Elderly Environment Estrogens Excision Fatty Acids Fatty acid glycerol esters Femur Floor Fluorescence Microscopy Fracture Gene Expression Gene Expression Profile Gene Expression Profiling Genes Genetic Glucose Glycolysis Healthcare Homeostasis Image Individual Knowledge Life Longevity Malignant Neoplasms Marrow Measures Menopause Mesenchymal Metabolic Metabolism Metric Microscope Mitochondria Modeling Molecular Molecular Profiling Mus Neurodegenerative Disorders Obesity Osteoblasts Osteocytes Osteogenesis Osteoporosis Ovariectomy Ovary Oxidative Phosphorylation Pathway interactions Physiological Physiology Play Population Prevalence Production Reactive Oxygen Species Rodent Model Role Sampling Staining method Stains Stromal Cells Sum Testing Therapeutic Time Withdrawal abdominal fat age related aging population bisphosphonate bone bone loss care burden cell type drug development economic impact high reward high risk in vivo inhibitor/antagonist insight mouse model novel strategies preference progenitor public health relevance response

项目摘要

DESCRIPTION (provided by applicant): Over the next thirty years there will be a dramatic shift in the demography of the aging population, with mean lifespan shifting to substantially older ages. This demographic shift will cause substantial increases in the aggregate health care burden, as the numbers of people suffering from age-related disease, including diseases relating to loss of bone, dramatically increase. Therefore, there is an urgent need to develop better treatments for mitigating bone loss in the elderly. Current therapeutics for age related bone loss such as the bisphosphonates, have been effective in reducing fractures in elderly subjects, but do not reverse the age- related decrease in bone formation and are associated with rare but significant side effects. The underlying mechanism responsible for the decline in bone formation with age currently remains unknown. That lack of a mechanistic understanding is confounded by additional gaps in our knowledge of whether cellular homeostasis is maintained in the cell types that regulate bone formation. The osteoblast is a one key cell type in maintaining bone, yet there is a tremendous deficit in our knowledge about what the bioenergetics are of the osteoblast in vivo, what the characteristic repertoire of genes being expressed within the cell is, and do these aspects of cell and molecular physiology change in response to bone loss. Our central hypothesis is "Loss of estrogen results in a fundamental shift in bioenergetic and gene expression profiles of osteoblasts isolated from cortical bone". Here, we propose two high-risk high-reward aims to investigate cell and molecular physiology in single cells isolated from mouse femurs in a popular model of bone loss; the ovariectomized mouse.

描述（由申请人提供）：在接下来的三十年里，老龄化人口的人口结构将发生巨大变化，平均寿命将大幅转向老龄化。年龄。这种人口结构的变化将导致总体医疗保健负担大幅增加，因为患有与年龄相关的疾病（包括与骨质流失有关的疾病）的人数急剧增加。因此，迫切需要开发更好的治疗方法来减轻老年人的骨质流失。目前针对与年龄相关的骨质流失的治疗方法，例如双磷酸盐，已有效减少老年受试者的骨折，但不能逆转与年龄相关的骨形成减少，并且与罕见但显着的副作用相关。目前尚不清楚骨形成随着年龄增长而下降的潜在机制。由于我们对调节骨形成的细胞类型是否维持细胞稳态的认识存在额外的空白，因此缺乏对机制的理解。成骨细胞是维持骨骼的一种关键细胞类型，但我们对成骨细胞在体内的生物能学是什么、细胞内表达的基因的特征库是什么以及这些方面的了解还存在巨大的缺陷。细胞和分子生理学因骨质流失而发生变化。我们的中心假设是“雌激素的丧失导致从皮质骨中分离出的成骨细胞的生物能和基因表达谱发生根本性转变”。在这里，我们提出了两个高风险高回报的目标，以在流行的骨质流失模型中研究从小鼠股骨中分离的单细胞的细胞和分子生理学；切除卵巢的小鼠。