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Expression, signaling, and function of P2X7 receptors in bone

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Abstract

Nucleotides released from cells in response to mechanical stimulation or injury may serve as paracrine regulators of bone cell function. Extracellular nucleotides bind to multiple subtypes of P2 receptors on osteoblasts (the cells responsible for bone formation) and osteoclasts (cells with the unique ability to resorb mineralized tissues). Both cell lineages express the P2X7 receptor subtype. The skeletal phenotype of mice with targeted disruption of P2rx7 points to interesting roles for this receptor in the regulation of bone formation and resorption, as well as the response of the skeleton to mechanical stimulation. This paper reviews recent work on the expression of P2X7 receptors in bone, their associated signal transduction mechanisms and roles in regulating bone formation and resorption. Areas for future research in this field are also discussed.

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Abbreviations

BzATP:

2′,3′-O-(4-benzoylbenzoyl)-ATP

[Ca2+]i :

cytosolic free Ca2+ concentration

ERK:

extracellular signal-regulated kinase

LPA:

lysophosphatidic acid

M-CSF:

macrophage colony-stimulating factor

NFAT:

nuclear factor of activated T cells

NF-κB:

nuclear factor κB

OPG:

osteoprotegerin

Osx:

Osterix

PLA2 :

phospholipase A2

PLD:

phospholipase D

PGE2 :

prostaglandin E2

PKC:

protein kinase C

RANK:

receptor activator of NF-κB

Runx2:

runt-related transcription factor-2

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Acknowledgments

We thank investigators in this rapidly advancing field for permission to reproduce illustrative material from their previously published work. We thank Frank Beier, Graeme Hunter, Dale Laird and Danielle Lapierre for constructive comments on the manuscript. Studies from the authors’ laboratories that were reviewed in this chapter were supported by the Canadian Institutes of Health Research (CIHR). M. Grol is supported by a CIHR Canada Graduate Scholarship and J. Korcok by the CIHR Network for Oral Research Training and Health.

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  1. CIHR Group in Skeletal Development and Remodeling, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON, Canada

    Matthew W. Grol, Nattapon Panupinthu, Jasminka Korcok, Stephen M. Sims & S. Jeffrey Dixon

  2. Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON, Canada, N6A 5C1

    S. Jeffrey Dixon

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  1. Matthew W. Grol
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Grol, M.W., Panupinthu, N., Korcok, J. et al. Expression, signaling, and function of P2X7 receptors in bone. Purinergic Signalling 5, 205–221 (2009). https://doi.org/10.1007/s11302-009-9139-1

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  • DOI: https://doi.org/10.1007/s11302-009-9139-1

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