[Frontiers in Bioscience S3, 1038-1046, June 1, 2011]

Bone phenotypes of P2 receptor knockout mice

Isabel Orriss1, Susanne Syberg2, Ning Wang3, Bernard Robaye4, Alison Gartland3, Niklas Jorgensen2, Tim Arnett1, Jean-Marie Boeynaems4

1Department of Cell and Developmental Biology, University College London, UK, 2Research Center of Ageing and Osteoporosis, Department of Medicine, Copenhagen University Hospital Glostrup, Denmark, 3Mellanby Centre for Bone Research, The University of Sheffield, UK, 4Institute of Interdisciplinary Research (IRIBHM), School of Medicine, Free University of Brussels (ULB), Belgium


1. Abstract
2. Introduction
3. Bone phenotypes of P2X7-/- mice
4. Bone phenotype of P2Y1-/- mice
5. Bone phenotype of P2Y2-/- mice
6. Preliminary results in P2Y6-/- mice
7. Preliminary results in P2Y13-/- mice
8. Summary and perspective
9. Acknowledgements
10. References


The action of extracellular nucleotides is mediated by ionotropic P2X receptors and G-protein coupled P2Y receptors. The human genome contains 7 P2X and 8 P2Y receptor genes. Knockout mice strains are available for most of them. As their phenotypic analysis is progressing, bone abnormalities have been observed in an impressive number of these mice: distinct abnormalities in P2X7-/- mice, depending on the gene targeting construct and the genetic background, decreased bone mass in P2Y1-/- mice, increased bone mass in P2Y2-/- mice, decreased bone resorption in P2Y6-/- mice, decreased bone formation and bone resorption in P2Y13-/- mice. These findings demonstrate the unexpected importance of extracellular nucleotide signalling in the regulation of bone metabolism via multiple P2 receptors and distinct mechanisms involving both osteoblasts and osteoclasts.