权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

The impact of neutrophil extracellular traps on bone remodeling and regeneration in health and disease

中性粒细胞胞外陷阱对健康和疾病中骨重塑和再生的影响

基本信息

批准号：
532492601
负责人：
Professor Dr. Johannes Keller, Ph.D.
金额：
--
依托单位：
Sektion Experimentelle Unfallchirurgie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
资助国家：
德国
起止时间：
项目状态：
未结题

来源：
https://gepris.dfg.de/gepris/projekt/532492601?language=en
关键词：
impact neutrophil extracellular traps bone

项目摘要

The interplay between bone and immune cells is central to maintaining bone integrity and governing regeneration after injury. Impaired bone remodeling and regeneration are highly relevant disorders caused by imbalanced activities of bone-forming osteoblasts and bone-resorbing osteoclasts, which are often associated with neutrophil dysfunction. Here, our preliminary data suggest that 'neutrophil extracellular traps' (NETs), an evolutionarily conserved defense mechanism designed to kill bacteria, profoundly affect bone biology. We hypothesize that neutrophils sense microscopic and macroscopic bone injury and orchestrate bone cell differentiation and function through NETs release (NETosis). The project will define how NETosis is induced by bone-derived factors and how NETs components affect bone formation and resorption. Physiological and pathophysiological models of bone remodeling and regeneration will be studied in mice with impaired NETs formation or resolution. Proteomics of shed NETs components in vitro and in vivo will be combined with specific assay systems to identify key skeletal mediators and further test their function. Overall, this project will explore a novel crosstalk between the innate immune system and bone biology with high clinical relevance.

骨骼和免疫细胞之间的相互作用对于维持骨骼完整性和控制损伤后的再生至关重要。骨重塑和再生受损是由骨形成成骨细胞和骨吸收破骨细胞活性不平衡引起的高度相关的疾病，通常与中性粒细胞功能障碍有关。在这里，我们的初步数据表明，“中性粒细胞胞外陷阱”（NET）是一种进化上保守的防御机制，旨在杀死细菌，深刻影响骨生物学。我们假设中性粒细胞感知微观和宏观骨损伤，并通过 NET 释放 (NETosis) 协调骨细胞分化和功能。该项目将定义骨源性因子如何诱导 NETosis 以及 NET 成分如何影响骨形成和吸收。将在 NET 形成或分解受损的小鼠中研究骨重塑和再生的生理学和病理生理学模型。脱落的 NET 成分的体外和体内蛋白质组学将与特定的检测系统相结合，以识别关键的骨骼介质并进一步测试其功能。总体而言，该项目将探索先天免疫系统和骨生物学之间具有高度临床相关性的新型串扰。