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The effects of P2X7 receptor antagonists on the formation and function of human osteoclasts in vitro

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Abstract

The P2X7 receptor (P2X7R) has been implicated in the process of multinucleation and cell fusion. We have previously demonstrated that blockade of P2X7Rs on osteoclast precursors using a blocking antibody inhibited multinucleated osteoclast formation in vitro, but that P2X7R KO mice maintain the ability to form multinucleated osteoclasts. This apparent contradiction of the role the P2X7R plays in multinucleation has prompted us to examine the effect of the most commonly used and recently available P2X7R antagonists on osteoclast formation and function. When added to recombinant RANKL and M-CSF human blood monocytes cultures, all but one compound, decreased the formation and function of multinucleated TRAP-positive osteoclasts in a concentration-dependent manner. These data provide further evidence for the role of the P2X7R in the formation of functional human multinucleated osteoclasts and highlight the importance of selection of antagonists for use in long-term experiments.

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Acknowledgments

The authors thank the Arthritis Research Campaign for funding (KAB, ref G0566). AA, AG and JAG were kindly supported by the European Commission under the 7th Framework Programme (proposal #202231) performed as a collaborative project among the members of the ATPBone Consortium (Copenhagen University, University College London, University of Maastricht, University of Ferrara, University of Liverpool, University of Sheffield, and Université Libre de Bruxelles), and is a sub study under the main study “Fighting osteoporosis by blocking nucleotides: purinergic signalling in bone formation and homeostasis”. We would also like to thank Dr. W.B. Bowler for his support of this project.

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Authors and Affiliations

  1. Academic Unit of Bone Biology, Mellanby Centre for Bone Research, Department of Human Metabolism, The University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, UK

    Ankita Agrawal & Alison Gartland

  2. Human Bone Cell Research Group, Department of Human Anatomy and Cell Biology, Biomedical Sciences, The University of Liverpool, The Sherrington Buildings, Ashton Street, L69 3GE, Liverpool, UK

    Katherine A. Buckley & James A. Gallagher

  3. AstraZeneca R&D Charnwood, Discovery BioScience, Bakewell Road, Loughborough, Leicestershire, LE11 5RH, UK

    Keith Bowers

  4. AstraZeneca R&D Charnwood, Medicinal Chemistry, Bakewell Road, Loughborough, Leicestershire, LE11 5RH, UK

    Mark Furber

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  1. Ankita Agrawal
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Correspondence to Alison Gartland.

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Agrawal, A., Buckley, K.A., Bowers, K. et al. The effects of P2X7 receptor antagonists on the formation and function of human osteoclasts in vitro. Purinergic Signalling 6, 307–315 (2010). https://doi.org/10.1007/s11302-010-9181-z

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  • DOI: https://doi.org/10.1007/s11302-010-9181-z

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