NGF-p75 信号在骨修复过程中协调骨骼细胞迁移。
NGF-p75 signaling coordinates skeletal cell migration during bone repair.
机构信息
Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA.
Department of Orthopaedics, Johns Hopkins University, Baltimore, MD 21205, USA.
出版信息
Sci Adv. 2022 Mar 18;8(11):eabl5716. doi: 10.1126/sciadv.abl5716.
Bone regeneration following injury is initiated by inflammatory signals and occurs in association with infiltration by sensory nerve fibers. Together, these events are believed to coordinate angiogenesis and tissue reprogramming, but the mechanism of coupling immune signals to reinnervation and osteogenesis is unknown. Here, we found that nerve growth factor (NGF) is expressed following cranial bone injury and signals via p75 in resident mesenchymal osteogenic precursors to affect their migration into the damaged tissue. Mice lacking in myeloid cells demonstrated reduced migration of osteogenic precursors to the injury site with consequently delayed bone healing. These features were phenocopied by mice lacking in osteoblast precursors. Single-cell transcriptomics identified mesenchymal subpopulations with potential roles in cell migration and immune response, altered in the context of deletion. Together, these results identify the role of p75 signaling pathway in coordinating skeletal cell migration during early bone repair.
骨损伤后的再生是由炎症信号启动的,与感觉神经纤维的浸润有关。人们认为这些事件共同协调血管生成和组织重编程,但免疫信号与再神经支配和成骨耦联的机制尚不清楚。在这里,我们发现神经生长因子 (NGF) 在颅骨损伤后表达,并通过 p75 在常驻间充质成骨前体中发出信号,影响其向损伤组织迁移。骨髓细胞中缺乏 的小鼠表现出成骨前体向损伤部位迁移减少,导致骨愈合延迟。这些特征与成骨前体中缺乏 的小鼠相似。单细胞转录组学鉴定出具有细胞迁移和免疫反应潜力的间充质亚群,在 缺失的情况下发生改变。总之,这些结果确定了 p75 信号通路在协调早期骨修复过程中骨骼细胞迁移中的作用。