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

Ankita Agrawal, Katherine A Buckley, Keith Bowers

    Purinergic Signalling
    |November 25, 2010
    PubMed

    Insights

    The P2X7 receptor (P2X7R) is crucial for forming multinucleated osteoclasts. P2X7R antagonists effectively inhibit osteoclast formation and function in human monocytes, underscoring the need for careful drug selection.

    Area of Science:

    • Immunology
    • Cell Biology
    • Pharmacology

    Background:

    • The P2X7 receptor (P2X7R) is involved in cell fusion and multinucleation.
    • Previous studies showed conflicting results regarding P2X7R's role in osteoclast formation.

    Purpose of the Study:

    • To investigate the effect of P2X7R antagonists on human osteoclast formation and function.
    • To resolve discrepancies in the literature concerning P2X7R's role in multinucleation.

    Main Methods:

    • Human blood monocytes were cultured with RANKL and M-CSF.
    • Various P2X7R antagonists were added to assess their impact on osteoclastogenesis.
    • Multinucleated TRAP-positive osteoclasts were quantified and their function evaluated.

    Main Results:

    • Most P2X7R antagonists significantly decreased the formation and function of multinucleated osteoclasts in a dose-dependent manner.
    • One antagonist showed no inhibitory effect, suggesting differential mechanisms or specificities.
    • These findings confirm P2X7R's role in generating functional human osteoclasts.

    Conclusions:

    • The P2X7 receptor plays a significant role in the formation of functional human multinucleated osteoclasts.
    • The choice of P2X7R antagonist is critical for experimental outcomes, especially in long-term studies.
    • Further research is needed to understand the differential effects of various antagonists.
    Keywords:
    ATPFormationFusionOsteoclastP2 receptorP2X7Resorption

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