Extracellular nucleotide signaling: a mechanism for integrating local and systemic responses in the activation of bone remodeling.

Abstract:

:Bone turnover occurs at discreet sites in the remodeling skeleton. The focal nature of this process indicates that local cues may facilitate the activation of bone cells by systemic factors. Nucleotides such as adenosine triphosphate (ATP) are locally released, short-lived, yet potent extracellular signaling molecules. These ligands act at a large family of receptors-the P2 receptors, which are subdivided into P2Y and P2X subtypes based on mechanism of signal transduction. Nucleotides enter the extracellular milieu via non-lytic and lytic mechanisms where they activate multiple P2 receptor types expressed by both osteoblasts and osteoclasts. In this review the release of ATP by bone cells is discussed in the context of activation of bone remodeling. We provide compelling evidence that nucleotides, acting via P2Y receptors, are potent potentiators of parathyroid hormone-induced signaling and transcriptional activation in osteoblasts. The provision of a mechanism to induce activation of osteoblasts above a threshold attained by systemic factors alone may facilitate focal remodeling and address the paradox of why systemic regulators like PTH exert effects at discreet sites.

journal_name

Bone

journal_title

Bone

authors

Bowler WB,Buckley KA,Gartland A,Hipskind RA,Bilbe G,Gallagher JA

doi

10.1016/s8756-3282(01)00430-6

subject

Has Abstract

pub_date

2001-05-01 00:00:00

pages

507-12

issue

5

eissn

8756-3282

issn

1873-2763

pii

S8756328201004306

journal_volume

28

pub_type

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