Temporal-spatial Regulation of MSCs by IGF-1

IGF-1 对 MSC 的时空调节

基本信息

  • 批准号:
    8845516
  • 负责人:
  • 金额:
    $ 13.13万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2014
  • 资助国家:
    美国
  • 起止时间:
    2014-05-06 至 2019-04-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Osteoporosis is a major bone disorder that affects both men and women during aging. The pathogenesis is not only due to the increased osteoclast activity in bone resorption, but also a decrease in bone formation mostly attributed to an insufficient supply of osteoblasts in the aged. Osteoblasts are non-replicative cells derived from the mesenchymal stem cell (MSC) lineage. We hypothesize that the pattern of acquisition of bone mass during childhood, maintenance in adulthood, and loss with aging is due to decreased osteoblast availability for bone formation as MSCs lose/slow their ability to differentiate into osteoblasts with aging. Insulin like growth factor type 1 (IGF-1) is known to stimulate osteoblastic differentiation by activation of mammalian target of rapamycin to maintain proper bone microarchitecture and mass. Thus, a series of experiments and animal models are designed to confirm the hypothesis that MSC differentiation slows with aging, mediated by down- regulation of the IGF-1 signaling pathway. The first aim is to determine the temporal-spatial regulation of MSC differentiation into mature osteoblasts in young, adult, and old mice using a MSC lineage tracing mouse model. The second aim is to dissect how the IGF-1 signaling pathway is regulated during the lifespan and affects the fate of MSCs. The goal of the proposed study is to identify the rate limiting steps in the differentiation process so that future therapies can be targeted at these essential steps. This project will be conducted by Dr. Janet Crane under the guidance of Dr. Xu Cao in the Department of Orthopaedic Surgery at Johns Hopkins University. Dr. Crane, a Pediatric Endocrinologist, is dedicated to a career in academia using basic and translational research to study factors affecting bone formation. Dr. Cao has an exceptional research career in bone biology using in vivo mouse models to study signaling mechanisms by which bone marrow MSCs contribute to bone homeostasis and remodeling, which will provide Dr. Crane with the training necessary to initiate her career as an independent investigator. The available resources and strong ongoing collaborative arrangements within the Department of Orthopaedic Surgery, the Division of Pediatric Endocrinology, and the Department of Neuroscience provide a rich learning environment and are completely supportive of the academic advancement of Dr. Crane.
描述(由申请人提供):骨质疏松症是一种主要的骨骼疾病,在衰老过程中影响男性和女性。其发病机制不仅是由于破骨细胞在骨吸收中的活性增加,而且由于成骨细胞供应不足而导致骨形成减少。成骨细胞是来源于间充质干细胞(MSC)谱系的非复制性细胞。我们假设,儿童时期骨量的获得、成年后的维持以及随着年龄的增长而丢失的模式是由于成骨细胞对骨形成的可用性降低,因为MSC随着年龄的增长而失去/减缓其分化成成骨细胞的能力。已知胰岛素样生长因子1(IGF-1)通过激活雷帕霉素的哺乳动物靶标来刺激成骨细胞分化,以维持适当的骨微结构和质量。因此,设计了一系列实验和动物模型来证实MSC分化随着衰老而减慢的假设,这是由IGF-1信号传导途径的下调介导的。第一个目的是确定MSC分化为成熟的成骨细胞在年轻,成年和老年小鼠使用MSC谱系示踪小鼠模型的时间-空间调节。第二个目的是剖析IGF-1信号通路在生命周期中是如何调节的,并影响MSC的命运。拟议研究的目标是确定分化过程中的限速步骤,以便将来 治疗可以针对这些基本步骤。本项目将由Janet起重机博士在约翰霍普金斯大学矫形外科曹旭博士的指导下进行。起重机,儿科内分泌学家,致力于在学术界的职业生涯,使用基础和转化研究,研究影响骨形成的因素。Cao博士在骨生物学领域拥有出色的研究生涯,使用体内小鼠模型研究骨髓MSC促进骨稳态和重塑的信号机制,这将为起重机博士提供必要的培训,以开始她作为独立研究者的职业生涯。骨科、儿科内分泌科和神经科学系内的现有资源和强有力的持续合作安排提供了丰富的学习环境,并完全支持起重机博士的学术进步。

项目成果

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会议论文数量(0)
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Janet Crane其他文献

Janet Crane的其他文献

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{{ truncateString('Janet Crane', 18)}}的其他基金

PTH Attenuation of Spinal Degeneration During Aging PI Janet Crane
PTH 对衰老过程中脊柱退化的衰减 PI Janet Crane
  • 批准号:
    10326803
  • 财政年份:
    2021
  • 资助金额:
    $ 13.13万
  • 项目类别:
PTH Attenuation of Spinal Degeneration During Aging PI Janet Crane
PTH 对衰老过程中脊柱退化的衰减 PI Janet Crane
  • 批准号:
    10556418
  • 财政年份:
    2021
  • 资助金额:
    $ 13.13万
  • 项目类别:
Role of glucocorticoid-suppression of preosteoclast PDGF-BB in skeletal angiogenesis
糖皮质激素抑制前破骨细胞 PDGF-BB 在骨骼血管生成中的作用
  • 批准号:
    10594402
  • 财政年份:
    2021
  • 资助金额:
    $ 13.13万
  • 项目类别:
Role of glucocorticoid-suppression of preosteoclast PDGF-BB in skeletal angiogenesis
糖皮质激素抑制前破骨细胞 PDGF-BB 在骨骼血管生成中的作用
  • 批准号:
    10368973
  • 财政年份:
    2021
  • 资助金额:
    $ 13.13万
  • 项目类别:
Role of glucocorticoid-suppression of preosteoclast PDGF-BB in skeletal angiogenesis
糖皮质激素抑制前破骨细胞 PDGF-BB 在骨骼血管生成中的作用
  • 批准号:
    10179554
  • 财政年份:
    2021
  • 资助金额:
    $ 13.13万
  • 项目类别:
PTH Attenuation of Spinal Degeneration During Aging PI Janet Crane
PTH 对衰老过程中脊柱退化的衰减 PI Janet Crane
  • 批准号:
    10090197
  • 财政年份:
    2021
  • 资助金额:
    $ 13.13万
  • 项目类别:
Temporal-spatial Regulation of MSCs by IGF-1
IGF-1 对 MSC 的时空调节
  • 批准号:
    9312113
  • 财政年份:
    2014
  • 资助金额:
    $ 13.13万
  • 项目类别:

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