Unraveling Mechanisms Driving Female-Specific Osteogenesis after Disrupting a Brain-to-Bone Circuit
揭示破坏脑到骨回路后驱动女性特异性成骨的机制
基本信息
- 批准号:9977658
- 负责人:
- 金额:$ 13.04万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-05-01 至 2025-03-31
- 项目状态:未结题
- 来源:
- 关键词:AdultAffectAgingAmericanAutomobile DrivingBiological AssayBlood CirculationBone DensityBone DiseasesBone GrowthBone callusBrainCartilageCell Differentiation processCell LineageCellsCenters for Disease Control and Prevention (U.S.)ChemicalsClinicalDataDiseaseEstrogen ReceptorsEstrogensFemaleFractureFutureGeneticGoalsHealthHigh Pressure Liquid ChromatographyHypothalamic structureImplantIn VitroLaboratoriesMass Spectrum AnalysisMenopauseMentorsMetabolismModelingMolecularMusNatureNeuronsOsteoblastsOsteogenesisOsteoidOsteoporosisOsteoporoticPeripheralPhasePlasmaReceptor SignalingRiskRunningSex DifferencesSignal TransductionSkeletonStem cell transplantStructure of nucleus infundibularis hypothalamiTechniquesTestingTherapeuticTibial FracturesTrainingTransplantationWomanWorkage relatedagedarmbonebone agingbone lossbone massbone strengthenergy balancefast protein liquid chromatographyimprovedlong bonemalemenmouse modelmutantosteogenicosteoporotic bonepreventrepairedresponsesexskeletalstem cell fatestem cellstherapy outcometibiatransplant model
项目摘要
ABSTRACT
Estrogen is a critical regulator of energy balance and skeletal metabolism. Women spend more than 1/3 of their
lives in an estrogen depleted state; drastically increasing their risk for age-related bone diseases such as
osteoporosis and fractures. Recent work by our lab and others demonstrates that loss of central estrogen
signaling in the arcuate nucleus (ARC) of the hypothalamus results in a female-specific elevation in bone mass
and strength, however molecular mechanisms that govern those responses are still unknown. I hypothesize that
deletion of ERa in the ARC of Esr1Nkx2-1Cre and ERaKOARC female mice releases a humoral brain-dependent
osteogenic factor (BDOF) which inherently changes resident SSCs, fating these cells for osteogenesis, and that
the changed SSCs are sufficient to enhance fracture repair and reverse bone loss in osteoporotic and
aged mouse models. For this project I will 1) use an unstabilized tibia fracture model to ask if Esr1Nkx2-1Cre
females have enhanced fracture repair. 2) I will use my new bioassay to test HPLC/FPLC fractionated mouse
plasma to identify and purify the BDOF, and 3) I will identify the molecular signals driving osteoblast expansion
in female mutants using a mutant-derived SSC transplant model. Answering these questions is critical for
the advancement of therapeutics for bone-related diseases in women and men.
摘要
雌激素是能量平衡和骨骼新陈代谢的重要调节器。女性将超过1/3的
生活在雌激素耗竭的状态;极大地增加了他们患与年龄相关的骨病的风险,如
骨质疏松症和骨折。我们实验室和其他人最近的研究表明,中枢雌激素的丢失
下丘脑弓状核(ARC)中的信号导致女性特有的骨量升高
和强度,然而,支配这些反应的分子机制仍不清楚。我假设
Esr1Nkx2-1Cre和ERaKOARC雌性小鼠ARC中ERA的缺失释放了体液脑依赖
成骨因子(BDOF),它固有地改变驻留的SSCs,使这些细胞成骨,并且
改变的SSCs足以促进骨质疏松和骨丢失的骨折修复和逆转骨丢失
老化的小鼠模型。对于这个项目,我将1)使用一个不稳定的胫骨骨折模型来询问Esr1Nkx2-1Cre
女性的骨折修复能力更强。2)我将用我的新生物检验法来测试高效液相/FPLC分离的小鼠
血浆鉴定和纯化BDOF,以及3)我将鉴定驱动成骨细胞扩张的分子信号
在使用突变体衍生的SSC移植模型的雌性突变体中。回答这些问题对于
女性和男性骨相关疾病的治疗进展。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Candice Herber其他文献
Candice Herber的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Candice Herber', 18)}}的其他基金
Unraveling Mechanisms Driving Female-Specific Osteogenesis after Disrupting a Brain-to-Bone Circuit
揭示破坏脑到骨回路后驱动女性特异性成骨的机制
- 批准号:
10152486 - 财政年份:2020
- 资助金额:
$ 13.04万 - 项目类别:
相似海外基金
Hormone therapy, age of menopause, previous parity, and APOE genotype affect cognition in aging humans.
激素治疗、绝经年龄、既往产次和 APOE 基因型会影响老年人的认知。
- 批准号:
495182 - 财政年份:2023
- 资助金额:
$ 13.04万 - 项目类别:
Parkinson's disease and aging affect neural activation during continuous gait alterations to the split-belt treadmill: An [18F] FDG PET Study.
帕金森病和衰老会影响分体带跑步机连续步态改变期间的神经激活:[18F] FDG PET 研究。
- 批准号:
400097 - 财政年份:2019
- 资助金额:
$ 13.04万 - 项目类别:
The elucidation of the mechanism by which intestinal epithelial cells affect impaired glucose tolerance during aging
阐明衰老过程中肠上皮细胞影响糖耐量受损的机制
- 批准号:
19K09017 - 财政年份:2019
- 资助金额:
$ 13.04万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Does aging of osteocytes adversely affect bone metabolism?
骨细胞老化会对骨代谢产生不利影响吗?
- 批准号:
18K09531 - 财政年份:2018
- 资助金额:
$ 13.04万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Links between affect, executive function, and prefrontal structure in aging: A longitudinal analysis
衰老过程中情感、执行功能和前额叶结构之间的联系:纵向分析
- 批准号:
9766994 - 财政年份:2018
- 资助金额:
$ 13.04万 - 项目类别:
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
- 批准号:
9320090 - 财政年份:2017
- 资助金额:
$ 13.04万 - 项目类别:
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
- 批准号:
10166936 - 财政年份:2017
- 资助金额:
$ 13.04万 - 项目类别:
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
- 批准号:
9761593 - 财政年份:2017
- 资助金额:
$ 13.04万 - 项目类别:
Experimental Model of Depression in Aging: Insomnia, Inflammation, and Affect Mechanisms
衰老过程中抑郁症的实验模型:失眠、炎症和影响机制
- 批准号:
9925164 - 财政年份:2016
- 资助金额:
$ 13.04万 - 项目类别:
Experimental Model of Depression in Aging: Insomnia, Inflammation, and Affect Mechanisms
衰老过程中抑郁症的实验模型:失眠、炎症和影响机制
- 批准号:
9345997 - 财政年份:2016
- 资助金额:
$ 13.04万 - 项目类别: