Osteoprogenitor mobilization for bone development and repair

骨祖细胞动员以促进骨骼发育和修复

基本信息

批准号：
10614547
负责人：
Joel D Boerckel
金额：
$ 34.54万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10614547
关键词：
Affect Bone Development Bone Transplantation Bone callus Breeding Cartilage Cell Proliferation Cells Clinical Collagen Collagen Gene Complication Cytoskeleton Data Defect Development Developmental Bone Diseases Embryo Environment Excision Feedback Fracture Genetic Transcription Goals Image Impairment In Vitro Intervention Knockout Mice Limb Development Limb structure Mechanics Mediating Mesenchymal Modeling Molecular Mus Natural regeneration Osteogenesis Pathway interactions Physiologic Ossification Positioning Attribute Primary Ossification Center Process Production Proliferating Proteins Qualifying Regulation Reporter Reporter Genes Research Role Testing Tissue Engineering Tissues Transcription Coactivator Transgenic Organisms Traumatic injury X-Ray Computed Tomography biomechanical test bone bone fracture repair bone repair cell motility clavicle combinatorial conditional knockout contrast enhanced design experimental study healing in vivo innovation insight intramembranous bone formation mechanical load mechanical signal mechanotransduction microCT migration osteoblast differentiation osteogenic osteoprogenitor cell progenitor programs recruit repaired sample fixation spatiotemporal stem cells success tumor

项目摘要

Abstract Large bone defects caused by traumatic injury or tumor resection pose a significant clinical challenge as they cannot not heal without intervention, and current bone grafting therapies are limited. Tissue engineering is a promising alternative, but is often limited by poor recruitment or supply of endogenous progenitor cells. Unlike large defects, bone fractures heal readily by recapitulating the steps of bone development. In fracture repair, mechanical cues, in the form of interfragmentary strains, are essential to determine the pathway by which bone formation occurs, namely direct bone formation through intramembranous ossification or indirect bone formation through endochondral ossification, in which a cartilage template forms first and is later replaced by bone. The mechanisms by which osteoprogenitor cells are mobilized during bone development and how mechanical cues direct fracture repair are poorly understood. We observed combinatorial roles of the mechanosensitive transcriptional co-activators, Yes-associated protein (YAP) and Transcriptional co-activator with PDZ-motif (TAZ) in promoting both bone development and repair. The goal of this application is to define the mechanistic roles of YAP/TAZ in osteoprogenitor cell mobilization during bone development and mechanical load-mediated fracture repair. Accomplishing this goal will provide new insights into developmental bone diseases, identify pathways that could be exploited to enhance healing, and position us to design new tissue engineering strategies that recapitulate the processes of bone development and natural repair for regeneration of large bone defects.

抽象的由于创伤性损伤或肿瘤切除引起的大骨缺损构成了重大的临床挑战没有干预就无法治愈，并且当前的骨移植疗法受到限制。组织工程是有希望的替代方案，但通常受到内源性祖细胞招募或供应不佳的限制。与众不同巨大的缺陷，骨骼骨折通过概括骨发育的步骤轻松愈合。在断裂修复中，机械提示，形式为腐败菌株，对于确定骨头的途径至关重要发生形成，即通过膜内骨化或间接骨形成骨形成通过内软骨骨化形成，在该骨化中首先形成软骨模板，然后替换为骨。在骨发育过程中动员了骨基因细胞的机制以及如何机械提示直接断裂修复知之甚少。我们观察到了机械敏感的转录共激活因子，与是相关的蛋白（YAP）和转录共激活因子与PDZ-MOTIF（TAZ）一起促进骨骼发育和修复。此应用的目的是定义 Yap/taz在骨发育和机械负荷介导的断裂修复。实现这一目标将为发展提供新的见解骨骼疾病，确定可以利用以增强愈合的途径，并定位我们设计新的途径概括骨发育和自然修复过程的组织工程策略大骨缺陷的再生。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Endothelial SMAD1/5 signaling couples angiogenesis to osteogenesis during long bone growth.

内皮 SMAD1/5 信号在长骨生长过程中将血管生成与成骨结合起来。

DOI：
10.1101/2023.01.07.522994
发表时间：
2023
期刊：
bioRxiv : the preprint server for biology
影响因子：
0
作者：
Lang,Annemarie;Benn,Andreas;Wolter,Angelique;Balcaen,Tim;Collins,Joseph;Kerckhofs,Greet;Zwijsen,An;Boerckel,JoelD
通讯作者：
Boerckel,JoelD