The mechanosensitive Piezo1 orchestrating angiogenesis is essential in bone fracture repair

Mechanical ion channel protein Piezo1 play vital roles in angiogenesis which has been proved to be high importance in varieties of biological processes. Bone formation in the fracture repair requires oxygen and nutrients from new blood vessels generated from fractured lesion. Understanding the underlying mechanisms linking angiogenesis and bone formation must be of great value for improved fracture healing. Here we employed mice with genetically modified endothelial specific depletion of Piezo1 channels to explore the hypothesis that Piezo1 is vital to the initiation of fracture healing. In this study, we demonstrated that Piezo1 expression and wide distribution along the bone and impaired endothelial Piezo1 channels result in derangements in bone fracture repair. Intriguingly, the calcium activated proteolytic caplain activity severely disrupted during vascularization, precluded osteoblast maturation and mineralization and subsequently the phosphorylated PI3K-AKT reduction. Furthermore, Piezo1 endothelial disruption impaired Notch signaling in bone union. These data collectively suggest that Piezo1 channels serve as a basis for clinical strategies to improve bone regeneration and treat delayed or nonunion in bone fracture.