LIVE IMAGING OF BONE REGENERATION IN ZEBRAFISH

斑马鱼骨再生的实时成像

基本信息

批准号：
10414209
负责人：
Stefano Di Talia
金额：
$ 3.18万
依托单位：
DUKE UNIVERSITY
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：
2020-02-01 至 2025-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10414209
关键词：
Adult Age American Behavior Biochemical Bone Diseases Bone Matrix Bone Regeneration Cells Cessation of life Chemicals Clinical Competence Complex Cues Dermal Embryo Ensure Epidermis Event Feedback Fracture Genetic Goals Growth Hypertrophy Image Individual Injury Jaw Life Limb structure Mechanics Mediating Methodology Mitogens Modeling Molecular Molecular Genetics Monitor Morphogenesis Natural regeneration Osteoblasts Pathway interactions Pattern Play Primordium Process Publishing Regenerative capacity Regulation Risk Role Signal Pathway Signal Transduction Skin Structure System Testing Tissues Training Transgenic Organisms Trauma Zebrafish base bone bone imaging cell behavior cell growth cell type economic impact experimental study genetic approach healing imaging modality imaging platform improved in vivo imaging limb amputation live cell imaging mechanotransduction migration regeneration potential regenerative growth response skin regeneration socioeconomics

项目摘要

ABSTRACT Mammalian bone has the capacity throughout life to regenerate in response to fracture injury. However, there is a ceiling for this regenerative potential, with hurdles to regeneration after a major trauma like limb amputation. This has a significant socio-economic impact, as it is estimated that at least one in two Americans over age 50 is expected to have or be at risk of bone disease, and every year an estimated 1.5 million individuals suffer a fracture due to bone disease. We have developed imaging methods to study how osteoblasts drive bone regeneration in zebrafish, which display robust regeneration after major injury to bony structures like their fins, scales, and jaws. Our goal is to exploit this regenerative capacity, new imaging platforms we have created, and the molecular genetic approaches available in zebrafish to improve our ability to understand and manipulate the regenerative capacity of bone. We have recently identified Erk signaling waves as a mechanism for the control of osteoblast regeneration. This Supplement application extends our original proposal by testing the hypothesis that mechanical signals contribute to osteoblast regeneration by integrating inputs from the Erk pathway and Hippo/Yap-Taz pathway, another signaling pathway playing crucial roles in bone morphogenesis and regeneration.

抽象的哺乳动物的骨骼在整个生命过程中都具有针对骨折损伤进行再生的能力。然而，有这种再生潜力的上限，在肢体截肢等重大创伤后再生会遇到障碍。这具有重大的社会经济影响，因为据估计，至少有二分之一的 50 岁以上的美国人预计患有骨病或面临骨病风险，每年估计有 150 万人患有骨病因骨病而骨折。我们开发了成像方法来研究成骨细胞如何驱动骨骼斑马鱼的再生能力，在鱼鳍等骨结构受到严重损伤后，斑马鱼表现出强大的再生能力，鳞片和下巴。我们的目标是利用这种再生能力、我们创建的新成像平台以及斑马鱼的分子遗传学方法可以提高我们理解和操纵斑马鱼的能力骨的再生能力。我们最近发现 Erk 信号波是一种控制机制成骨细胞再生。该补充应用程序通过测试假设扩展了我们最初的提议机械信号通过整合 Erk 通路的输入来促进成骨细胞再生， Hippo/Yap-Taz 通路是另一个在骨形态发生和骨形态发生中发挥关键作用的信号通路再生。