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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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