ArticleThe Journal of clinical investigation2012
The ADP receptor P2RY12 regulates osteoclast function and pathologic bone remodeling.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 101 citations in OpenAlex.
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- Modulation of osteoblast differentiation and function by the P2X4 receptor.Purinergic signalling · 2023Article
- The Signaling Pathway of the ADP Receptor P2YInternational journal of molecular sciences · 2023Review
- Increased expression of the P2YRenal failure · 2023Article
- Extracellular ATP and its derivatives provide spatiotemporal guidance for bone adaptation to wide spectrum of physical forces.Bone reports · 2022Review
- Protective Effects of Higher Exposure to Aspirin and/or Clopidogrel on the Occurrence of Hip Fracture among Diabetic Patients: A Retrospective Cohort Study.Biomedicines · 2022Article
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- Endothelium-specific depletion of LRP1 improves glucose homeostasis through inducing osteocalcin.Nature communications · 2021Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors at 5 institutions in 4 countries.
Funding
Abstract
The adenosine diphosphate (ADP) receptor P2RY12 (purinergic receptor P2Y, G protein coupled, 12) plays a critical role in platelet aggregation, and P2RY12 inhibitors are used clinically to prevent cardiac and cerebral thrombotic events. Extracellular ADP has also been shown to increase osteoclast (OC) activity, but the role of P2RY12 in OC biology is unknown. Here, we examined the role of mouse P2RY12 in OC function. Mice lacking P2ry12 had decreased OC activity and were partially protected from age-associated bone loss. P2ry12-/- OCs exhibited intact differentiation markers, but diminished resorptive function. Extracellular ADP enhanced OC adhesion and resorptive activity of WT, but not P2ry12-/-, OCs. In platelets, ADP stimulation of P2RY12 resulted in GTPase Ras-related protein (RAP1) activation and subsequent αIIbβ3 integrin activation. Likewise, we found that ADP stimulation induced RAP1 activation in WT and integrin β3 gene knockout (Itgb3-/-) OCs, but its effects were substantially blunted in P2ry12-/- OCs. In vivo, P2ry12-/- mice were partially protected from pathologic bone loss associated with serum transfer arthritis, tumor growth in bone, and ovariectomy-induced osteoporosis: all conditions associated with increased extracellular ADP. Finally, mice treated with the clinical inhibitor of P2RY12, clopidogrel, were protected from pathologic osteolysis. These results demonstrate that P2RY12 is the primary ADP receptor in OCs and suggest that P2RY12 inhibition is a potential therapeutic target for pathologic bone loss.
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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 OpenQuestion graph.