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

• Published in: Bone (New York, N.Y.) Vol. 28; no. 5; pp. 507 - 512
• Main Authors: Bowler, W.B, Buckley, K.A, Gartland, A, Hipskind, R.A, Bilbe, G, Gallagher, J.A
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-05-2001; Elsevier Science; Elsevier
• Subjects: Adenosine triphosphate (ATP); Adenosine Triphosphate - genetics; Adenosine Triphosphate - metabolism; Animals; Biochemistry, Molecular Biology; Biological and medical sciences; Bone Remodeling - genetics; c- fos; Extracellular Space - genetics; Extracellular Space - metabolism; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - physiology; Humans; Life Sciences; Nucleotides - genetics; Nucleotides - metabolism; Osteoblast; Osteoblasts - cytology; Osteoblasts - metabolism; P2 receptor; Parathyroid hormone (PTH); Receptors, Purinergic P2 - genetics; Receptors, Purinergic P2 - metabolism; Remodeling; Signal Transduction - genetics; Skeleton and joints; Vertebrates: osteoarticular system, musculoskeletal system; Osteoblast; Parathyroid hormone (PTH); Remodeling; c- fos; P2 receptor; Adenosine triphosphate (ATP); Human; Activation; Osteoclast; Systemic; Bone remodeling; Experimental study; Extracellular; Biological activity; Local effect; Osteoarticular system; Protein hormone; Parathormone; Signal transduction; Parathyroid hormone; Bone; ATP; Biological receptor; adenosine triphosphate (atp) osteoblast p2 receptor parathyroid hormone (pth) remodeling c-fos osteoblast-like cells arachidonic-acid release focal tyrosine kinase smooth-muscle cells c-fos protooncogene parathyroid-hormone protein-kinase endothelial-cells phospholipase-c receptor activation
• ISSN: 8756-3282; 1873-2763; 8756-3282
• DOI: 10.1016/S8756-3282(01)00430-6

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.