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Nucleotides and Regulation of Bone Cell Function

2006 Edition, September 27, 2006

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Active, Most Current

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ISBN: 978-0-8493-3368-2
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Product Details:

  • Revision: 2006 Edition, September 27, 2006
  • Published Date: September 27, 2006
  • Status: Active, Most Current
  • Document Language: English
  • Published By: CRC Press (CRC)
  • Page Count: 234
  • ANSI Approved: No
  • DoD Adopted: No

Description / Abstract:


ATP has long been recognized as an intracellular energy source, although acceptance of its role as an extracellular signaling molecule has taken considerably longer. The potent actions of ATP on the heart and blood vessels were first described in 1929.1 Some 40 years later, ATP, a purine, was proposed as a neurotransmitter in nonadrenergic, noncholinergic nerves in the gut and bladder and the word "purinergic" was coined.2 Separate families of receptors for adenosine (P1) and ATP and ADP (P2) were proposed in 1978.3 However, it was not until receptors for ATP and its ectoenzymatic breakdown product, adenosine, were cloned in the early 1990s that purinergic signaling became more widely accepted.4 Currently, four subtypes of P1 receptors, seven subtypes of P2X ionotropic receptors, and eight subtypes of P2Y metabotropic receptors are recognized.5–7

The field is now expanding rapidly and it is clear that receptors for purines and pyrimidines are widely distributed not only in the nervous system, but also in many nonneuronal cells.8 Both short-term purinergic signaling in neurotransmission, neuromodulation, exocrine and endocrine secretion, platelet aggregation, vascular endothelial cell-mediated vasodilatation, and nociceptive mechanosensory transduction; and long-term (trophic) purinergic signaling of cell proliferation, differentiation, migration, and death in embryological development, neural regeneration, cell turnover of epithelial cells in skin and visceral organs, wound healing, aging, and cancer have been described.9 The therapeutic potential of purinergic signalling for a wide variety of diseases is being explored.10

The work of Leong et al.11 demonstrated that extracellular ATP stimulated the breakdown of nasal cartilage in explant cultures, an effect that appeared to be mediated via P2 receptors.12 A role for extracellular purines in bone biology was first recognized in 1992, when Reimer and Dixon showed that ATP, ADP, and UTP elevated intracellular Ca2+ in osteoblasts (bone forming cells), suggesting mediation via two distinct P2 receptor subtypes.13 Subsequently, several laboratories have described functional effects of extracellular nucleotides on osteoclasts (bone resorbing cells) as well as on osteoblasts, and it has become apparent that these cells each express a range of both P2X and P2Y receptors.14–22 Useful reviews of the field are available.23–26 There has been increased interest and important advances made in this field, and the aim of the present volume is to bring together chapters by the leading figures to provide the reader with an account of the current status of purinergic signaling in bone, including pathophysiology and therapeutic potential.