Mechanosensitive Piezo1 in endothelial cells promotes angiogenesis to support bone fracture repair
Mechanosensitive Piezo1 in endothelial cells promotes angiogenesis to support bone fracture repair
复制标题
内皮细胞中的机械敏感性 Piezo1 促进血管生成以支持骨折修复
DOI：
10.1016/j.ceca.2021.102431
复制
发表时间：
2021-06-18
期刊：
影响因子：
4
通讯作者：
Li, Jing
中科院分区：
文献类型：
--
作者：
Chen, Peng;Zhang, Gangyu;Li, Jing
Piezo1是一种可通透钙离子的非选择性阳离子通道，能感知多细胞生物所受的机械刺激，介导包括血管生成在内的多种生物学过程。通过骨折损伤处新形成的血管来供应营养物质和氧气，这对骨折修复至关重要。阐明血管生成与骨修复相关的潜在机制，有助于促进骨折愈合。在此，研究人员利用内皮细胞特异性缺失Piezo1通道的小鼠，来探究Piezo1在骨折愈合起始阶段的作用。研究人员还对Piezo1在骨血管系统中的表达与分布情况进行了研究。内皮细胞Piezo1缺失会导致骨折修复受损、血管形成过程中钙激活的蛋白水解酶——钙蛋白酶活性下调、成骨细胞成熟与骨化受抑制、磷酸化的PI3K - AKT表达下调，以及骨折愈合过程中Notch信号传导受损。这些研究结果表明，Piezo1蛋白是促进骨再生以及治疗延迟愈合或不愈合骨折的潜在靶点。
Piezo1, a calcium-permeable non-selective cationic channel that senses mechanical stimulation in multicellular organisms, mediates various biological processes, including angiogenesis. The supply of nutrients and oxygen through newly formed blood vessels at the fractured lesion is critical for bone fracture repair. The elucidation of the underlying mechanisms involved in angiogenesis and bone repair can aid in improving fracture healing. Here, mice with endothelial cell-specific deletion of Piezo1 channels were used to examine the role of Piezo1 in the initiation of fracture healing. The expression and distribution of Piezo1 was explored in the vasculature of the bone. The deletion of endothelial Piezo1 resulted in impaired bone fracture repair, downregulation of calciumactivated proteolytic calpain activity during vascularization, inhibition of osteoblast maturation and ossification, downregulation of phosphorylated PI3K-AKT, and impaired Notch signaling during bone fracture union. These findings indicated that Piezo1 protein is a potential target for enhancing bone regeneration and treating delayed or nonunion bone fractures.