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 calcium-activated 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.

Piezo1 是一种钙渗透性非选择性阳离子通道，可感知多细胞生物体中的机械刺激，介导各种生物过程，包括血管生成。通过骨折病变处新形成的血管供应营养和氧气对于骨折修复至关重要。阐明血管生成和骨修复的潜在机制有助于改善骨折愈合。在这里，使用内皮细胞特异性删除Piezo1通道的小鼠来检查 Piezo1 在骨折愈合启动中的作用。研究人员探讨了 Piezo1 在骨血管系统中的表达和分布。内皮Piezo1的缺失导致骨折修复受损、血管形成过程中钙激活蛋白水解钙蛋白酶活性下调、成骨细胞成熟和骨化受到抑制、磷酸化 PI3K-AKT 下调以及骨折愈合过程中 Notch 信号传导受损。这些发现表明 Piezo1 蛋白是增强骨再生和治疗迟发性骨折或骨不连的潜在靶点。