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CROSSTALK BETWEEN HEDGEHOG AND IGF SIGNALING IN OSTEOPROGENITORS

骨祖细胞中 Hedgehog 和 IGF 信号传导之间的串扰

基本信息

批准号：
9303056
负责人：
Fanxin Long
金额：
$ 38.14万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-04-01 至 2021-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9303056
关键词：
Ablation Adult Amino Acids Anabolism Binding Biochemical Cell Lineage Cells Embryonic Development Erinaceidae Family Feedback Fracture GLI Family Protein Gene Targeting Genetic Genetic Transcription Gli2 protein Half-Life Homeostasis Human Knowledge Length Life Longevity Maintenance Mediating Medical Molecular Mus Osteoblasts Osteogenesis Osteoporosis Output Patients Phosphorylation Physiological Population Proteins Proto-Oncogene Proteins c-akt Publishing Regulation Reporting Role Signal Transduction Signaling Molecule Skeleton Source Stem cells System Testing Therapeutic Treatment Efficacy Work base bone experience experimental study fly gene induction in vivo insight long bone novel osteoblast differentiation osteogenic osteoprogenitor cell postnatal progenitor repaired skeletal smoothened signaling pathway stem substantia spongiosa transcription factor ubiquitin-protein ligase

项目摘要

Abstract A fundamental understanding of the molecular mechanism governing adult osteoprogenitors and their differentiation is essential for developing novel bone anabolic therapeutics. We have recently discovered that Hh signaling induces expression of Igf signaling components and activates Igf signaling, thus engaging in a Hh-Igf positive feedabck loop in osteoblast-lineage cells. In addition, we have identified a Hh-responsive population as critical osteoprogenitors in adult bones. In the current proposal, we will further elucidate the biochemical basis for the Hh-Igf feedback mechanism, and explore the physiological relevance of the regulatory loop in postnatal osteoprogenitors and adult bone formation. Overall, successful completion of this project will provide novel mechanistic insights about Hh-Igf signaling in adult bones, and may open new avenues for developing effective bone anabolic therapeutics.

摘要对成体骨祖细胞及其成骨细胞调控分子机制的基本认识分化是开发新的骨合成代谢疗法的关键。我们最近做了发现HH信号诱导IGF信号成分的表达并激活IGF 因此，在成骨细胞系细胞中参与了HH-IGF阳性摄食循环。此外，我们已经确定HH反应人群是成人骨骼中关键的骨祖细胞。在当前建议，我们将进一步阐明HH-IGF反馈机制的生化基础，以及探讨生后成骨细胞和成骨细胞调控环的生理学相关性骨形成。总体而言，该项目的成功完成将提供新的机械洞察力关于成人骨骼中的HH-IGF信号转导，并可能为开发有效的骨骼开辟新的途径合成代谢疗法。