Investigating the Impact of Social Isolation on Bone Metabolism

研究社会隔离对骨代谢的影响

• 批准号: 10722595
• 负责人: Rebecca Mountain
• 金额: $ 12.74万
• 依托单位: MAINEHEALTH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10722595
• 关键词: 11-beta-Hydroxysteroid Dehydrogenases; Adrenergic Agents; Affect; Anxiety; Architecture; Biological Markers; Bone Density; Bone Marrow; Bone Resorption; Brain; COVID-19 pandemic; Catecholamines; Clinical; Clinical Research; Clinical Treatment; Corticosterone; Data; Disease; Elderly; Exposure to; Female; Femur; Fracture; Future; Gene Expression; Genes; Genetic; Glucocorticoid Receptor; Glucocorticoids; Goals; Health; Histologic; Homeostasis; Human; Image; Individual; Knockout Mice; Loneliness; Long-Term Effects; Measures; Mediating; Mental Depression; Mental Health; Mental disorders; Metabolic; Metabolism; Metyrapone; MicroRNAs; Modeling; Molecular; Morbidity - disease rate; Mus; NADH dehydrogenase (ubiquinone); Osteogenesis; Osteoporosis; Outcome; Phase; Phenotype; Physiological; Populations at Risk; Prevalence; Prevention strategy; Propranolol; Proteomics; Psyche structure; Psychosocial Stress; Public Health; Research; Risk; Rodent; Role; Serum; Sex Differences; Signal Transduction; Social isolation; Stress; Sympathetic Nervous System; Testing; Thick; Time; Work; antagonist; beta-2 Adrenergic Receptors; biological sex; bone; bone health; bone loss; bone mass; bone metabolism; circulating microRNA; coping; epidemiology study; experience; fracture risk; genetic approach; human old age (65+); inhibitor; lonely individuals; male; miRNA expression profiling; mortality; mortality risk; mouse model; neural; novel; pharmacologic; prevent; receptor; receptor expression; response; sex; skeletal; stress disorder; substantia spongiosa; therapeutic target; treatment strategy

PROJECT SUMMARY Social isolation is a potent form of psychosocial stress, and a growing public health concern. Older adults, particularly those individuals isolated during the COVID-19 pandemic, are particularly vulnerable. One in four individuals over the age of 65 are estimated to be affected by social isolation and loneliness, which are associated with an increase in mortality risk by up to 70%. Previous studies have shown other forms of psychosocial stress and mental illness are associated with increased risk for osteoporosis and related fractures, which are likewise associated with increased mortality in older adults. Despite the increase in social isolation and the overlap between at-risk populations, there has been little research on the effects of social isolation on bone loss and skeletal metabolism. The limited work that has been done in rodents suggest that social isolation negatively impacts bone health, leading to decreased bone mineral density. None of these studies, however, have explored the mechanisms of isolation-induced bone loss, or examined differences in the effect of isolation on bone between the sexes. My own preliminary studies show that males exposed to social isolation had reduced femoral bone volume fraction, bone mineral density, and cortical thickness. Females, conversely, did not have any reduction in bone mass. My data also showed changes to glucocorticoid receptor and β2 adrenergic receptor expression as a result of social isolation, which both have known effects on bone. The goal of this project is therefore to test the overarching hypothesis that social isolation leads to bone loss through altered glucocorticoid (Aim 1) and sympathetic nervous system (Aim 2) activity. I will test these hypotheses using a 4 to 8-week-long mouse model of social isolation in 16-week old mice, in combination of pharmacological and genetic approaches. I will also use proteomic and microRNA sequencing approaches to identify novel systemic changes in response to social isolation that may impact bone. The proposed project will be the first study to identify mediating mechanisms of social isolation-induced bone loss and precisely test the effects of isolation on bone metabolism through a range of imaging, genetic, histologic, and omic approaches. The results of this project will inform future clinical and epidemiological studies, and help identify prevention strategies and treatments for individuals at the greatest risk for social isolation.

项目摘要 社会隔离是社会心理压力的一种潜在形式，也是日益增长的公共卫生问题。老年人， 特别是那些在19日大流行期间孤立的人特别容易受到伤害。四分之一 据估计，65岁以上的个人受社会隔离和孤独的影响， 与死亡率风险增加高达70％有关。以前的研究表明了其他形式的 社会心理压力和精神疾病与骨质疏松症和相关风险增加有关 裂缝，与老年人死亡率增加有关。尽管社会有所增加 隔离和处于危险人群之间的重叠，几乎没有关于社会影响的研究 分离骨质流失和骨骼代谢。在啮齿动物中所做的有限的工作表明 社会隔离对骨骼健康产生负面影响，导致骨矿物质密度降低。这些都不是 然而，研究探讨了隔离引起的骨质流失的机制，或检查了 隔离对性别之间骨骼的影响。我自己的初步研究表明，男性暴露于 社会隔离减少了股骨​​体积分数，骨矿物质密度和皮质厚度。 相反，女性的骨骼质量没有任何减少。我的数据还显示了变化 糖皮质激素受体和β2肾上腺素受体表达是由于社会隔离而导致的，这两者都有 对骨骼的已知影响。因此，该项目的目的是检验社会的总体假设 通过改变糖皮质激素（AIM 1）和交感神经系统（AIM 2），隔离导致骨质流失 活动。我将使用16周大的社交隔离鼠标模型来检验这些假设 小鼠，结合药物和遗传方法。我还将使用蛋白质组学和microRNA 测序方法以识别可能影响社会隔离的新型系统变化 骨。拟议的项目将是第一个确定社会隔离引起的中介机制的研究 通过一系列成像，遗传， 组织学和OMIC方法。该项目的结果将为未来的临床和流行病学提供信息 研究，并帮助确定针对社会风险最大的个人的预防策略和治疗 隔离。