ArticleThe Journal of cell biology2024
Purinergic signaling through the P2Y2 receptor regulates osteocytes' mechanosensitivity.
Article in The Journal of cell biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Construction and validation of a nomogram for the diagnosis of postmenopausal osteoporosis.Molecular medicine reports · 2026Article
- Purinergic signaling in osteoarthritis: Mechanistic insights into pathogenesis and therapeutic targeting.Genes & diseases · 2026Review
- ATP-P2X7R-NLRP3 Axis as a Unifying Mechanism of ATP-Induced Cell Death in Degenerative Bone and Cardiovascular Diseases.Journal of inflammation research · 2026Review
- A mechanobiological hypothesis on bone cement-induced progression of bone metastases.Frontiers in bioengineering and biotechnology · 2026Article
- Purinergic receptors play a key role in shock wave-induced proliferation.Scientific reports · 2025Article
Corrections and comments
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Authors and funding
8 authors.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.