Piezo1 expression in mature osteocytes is dispensable for the skeletal response to mechanical loading
Xuehua Li, Connie Zhang, Cameron E Vail, John T. Sherrill, Jinhu Xiong
Abstract
Mechanical loading is essential for bone growth and homeostasis, with osteocytes considered the primary mechanosensors. Deleting the mechanosensitive ion channel Piezo1 from Dmp1-Cre-targeted cells, which include both osteoblasts and osteocytes, resulted in reduced bone mass and impaired skeletal responses to mechanical stimuli. To specifically isolate Piezo1's role in osteocytes, we used Sost-Cre mice to generate mice with Piezo1 deletion exclusively in mature osteocytes. These mice exhibited lower bone mineral density, decreased cancellous bone mass, and reduced cortical thickness with decrease periosteal expansion. However, unlike mice lacking Piezo1 in both osteoblasts and osteocytes, those with Piezo1 deletion in mature osteocytes responded normally to mechanical loading. These findings suggest that Piezo1 expression in mature osteocytes contributes to bone maintenance under normal physiological condition, but is dispensable for the skeletal response to mechanical loading. • Piezo1 expression in Sost-Cre targeted mature osteocytes contributes to cancellous and cortical bone homeostasis. • Loss of Piezo1 in Sost-Cre targeted cells does not affect the skeletal response to mechanical loading. • Piezo1 upregulates Wnt1 expression via Ca 2+ /CaM/YAP signaling pathway.