Mechanosensitive Piezo1 Mediates Bone Fracture Repair by Promoting Angiogenesis Through Notch Signaling

Abstract

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. Funding Information: The study was supported by the National Natural Science Foundation of China (NSFC 81770453, 81774339, 81603641). Declaration of Interests: The authors have declared that no conflict of interest exists. Ethics Approval Statement: All animal studies were approved by the Animal Care and Use Committee of Guangzhou University of Chinese Medicine (Approval number: 2017030543).