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Journal of Osteoporosis
Volume 2012, Article ID 637986, 10 pages
http://dx.doi.org/10.1155/2012/637986
Research Article

Association between P2X7 Receptor Polymorphisms and Bone Status in Mice

1Research Centre of Ageing and Osteoporosis, Departments of Diagnostics and Medicine, Glostrup University Hospital, 2600 Glostrup, Denmark
2Osteoporosis and Bone Metabolic Unit, Departments of Endocrinology and Clinical Biochemistry, Hvidovre University Hospital, 2650 Hvidovre, Denmark
3Department of Internal Medicine, Washington University School of Medicine and the St. Louis Veterans Affairs Medical Center, St. Louis, MO 63110, USA

Received 31 March 2012; Accepted 28 May 2012

Academic Editor: Elena Adinolfi

Copyright © 2012 Susanne Syberg et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Macrophages from mouse strains with the naturally occurring mutation P451L in the purinergic receptor P2X7 have impaired responses to agonists (1). Because P2X7 receptors are expressed in bone cells and are implicated in bone physiology, we asked whether strains with the P451L mutation have a different bone phenotype. By sequencing the most common strains of inbred mice, we found that only a few strains (BALB, NOD, NZW, and 129) were harboring the wild allelic version of the mutation (P451) in the gene for the purinergic receptor P2X7. The strains were compared by means of dual energy X-ray absorptiometry (DXA), bone markers, and three-point bending. Cultured osteoclasts were used in the ATP-induced pore formation assay. We found that strains with the P451 allele (BALB/cJ and 129X1/SvJ) had stronger femurs and higher levels of the bone resorption marker C-telopeptide collagen (CTX) compared to C57Bl/6 (B6) and DBA/2J mice. In strains with the 451L allele, pore-formation activity in osteoclasts in vitro was lower after application of ATP. In conclusion, two strains with the 451L allele of the naturally occurring mutation P451L, have weaker bones and lower levels of CTX, suggesting lower resorption levels in these animals, which could be related to the decreased ATP-induced pore formation observed in vitro. The importance of these findings for the interpretation of the earlier reported effects of P2X7 in mice is discussed, along with strategies in developing a murine model for testing the therapeutic effects of P2X7 agonists and antagonists upon postmenopausal osteoporosis.