The effects of P2X7 receptor antagonists on the formation and function of human osteoclasts in vitro |
| |
| Authors: | Ankita Agrawal Katherine A Buckley Keith Bowers Mark Furber James A Gallagher Alison Gartland |
| |
| Institution: | (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;(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;(3) AstraZeneca R&D Charnwood, Discovery BioScience, Bakewell Road, Loughborough, Leicestershire, LE11 5RH, UK;(4) AstraZeneca R&D Charnwood, Medicinal Chemistry, Bakewell Road, Loughborough, Leicestershire, LE11 5RH, UK; |
| |
| 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. |
| |
| Keywords: | P2X7 ATP Osteoclast P2 receptor Resorption Formation Fusion |
| 本文献已被 PubMed SpringerLink 等数据库收录！ |
|
