Purinergic signaling through the P2Y2 receptor regulates osteocytes' mechanosensitivity
Recommended Citation
Chougule A, Zhang C, Vinokurov N, Mendez D, Vojtisek E, Shi C, Zhang J, and Gardinier J. Purinergic signaling through the P2Y2 receptor regulates osteocytes' mechanosensitivity. J Cell Biol 2024; 223(11).
Document Type
Article
Publication Date
11-4-2024
Publication Title
The Journal of cell biology
Abstract
Osteocytes' response to dynamic loading plays a crucial role in regulating the bone mass but quickly becomes saturated such that downstream induction of bone formation plateaus. The underlying mechanisms that downregulate osteocytes' sensitivity and overall response to loading remain unknown. In other cell types, purinergic signaling through the P2Y2 receptor has the potential to downregulate the sensitivity to loading by modifying cell stiffness through actin polymerization and cytoskeleton organization. Herein, we examined the role of P2Y2 activation in regulating osteocytes' mechanotransduction using a P2Y2 knockout cell line alongside conditional knockout mice. Our findings demonstrate that the absence of P2Y2 expression in MLO-Y4 cells prevents actin polymerization while increasing the sensitivity to fluid flow-induced shear stress. Deleting osteocytes' P2Y2 expression in conditional-knockout mice enabled bone formation to increase when increasing the duration of exercise. Overall, P2Y2 activation under loading produces a negative feedback loop, limiting osteocytes' response to continuous loading by shifting the sensitivity to mechanical strain through actin stress fiber formation.
Medical Subject Headings
Animals; Receptors, Purinergic P2Y2; Osteocytes; Mechanotransduction, Cellular; Mice, Knockout; Mice; Stress, Mechanical; Cell Line; Osteogenesis; Signal Transduction; Actins; Mice, Inbred C57BL
PubMed ID
39212624
Volume
223
Issue
11
