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

被引：37

作者：

Agrawal, Ankita ^{[1
]}

Buckley, Katherine A. ^{[2
]}

Bowers, Keith ^{[3
]}

Furber, Mark ^{[4
]}

Gallagher, James A. ^{[2
]}

Gartland, Alison ^{[1
]}

机构：

[1] Univ Sheffield, Dept Human Metab, Acad Unit Bone Biol, Mellanby Ctr Bone Res, Sheffield S10 2RX, S Yorkshire, England

[2] Univ Liverpool, Human Bone Cell Res Grp, Dept Human Anat & Cell Biol, Liverpool L69 3GE, Merseyside, England

[3] AstraZeneca R&D Charnwood, Discovery BioSci, Loughborough LE11 5RH, Leics, England

[4] AstraZeneca R&D Charnwood, Med Chem, Loughborough LE11 5RH, Leics, England

来源：

PURINERGIC SIGNALLING | 2010年 / 6卷 / 03期

关键词：

P2X7; ATP; Osteoclast; P2; receptor; Resorption; Formation; Fusion; P2X(7) RECEPTOR; EXTRACELLULAR ATP; POTENT ANTAGONIST; CELL-FORMATION; BONE; DIFFERENTIATION; ACTIVATION; OSTEOBLASTS; MACROPHAGES; MODULATION;

D O I：

10.1007/s11302-010-9181-z

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：307 / 315

页数：9

共 42 条

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