P2 receptor expression, signaling and function in osteoclasts

Abstract

Skeletal development and bone remodeling depend on the coordinated activity of osteoblasts and osteoclasts, which are responsible for bone formation and resorption, respectively. Mature osteoclasts result from the fusion of precursor cells, and they are large, multinucleated, highly specialized cells. Cellular release of ATP and UTP occurs in response to a variety of stimuli including mechanical stimulation, which occurs in the bone environment. ATP and UTP or their metabolites can then act on P2 receptors in the plasma membrane to induce various responses in bone cells. The influence of these receptors on osteoclast physiology and bone physiology in general is beginning to be understood, but much work is still required. This review focuses on P2 receptors in osteoclasts, their expression, signaling and function in the regulation of osteoclast formation, resorptive activity and survival.

Selective Induction of P2Y14 Receptor by RANKL Promotes Osteoclast Formation

“…Although a number of different P2Y receptors are functionally expressed in osteoclasts, it has been suggested that more P2Y receptors will play a role in osteoclast biology (Reyes et al, 2011). Moreover, whether the RANKL signal regulates expression of P2Y receptor has not yet reported.…”

“…Based on studies showing that nucleotides are released in bone in response to mechanical stimuli (Reyes et al, 2011;Wiebe et al, 1999), we examined transcriptional responses of known seven P2Y nucleotide receptors upon RANKL stimulation. As shown in Fig.…”

“…Specifically, Korcok et al (2005) investigated P2Y receptor expression by RT-PCR and showed that P2Y1, 2, and 6 receptors are expressed by rabbit osteoclasts. Agonists of P2Y1, such as ADP, ADPβS and 2-MeSADP, induce Ca 2+ responses in osteoclasts and extracellular ADP enhances osteoclastic resorption (Hoebertz et al, 2001;Reyes et al, 2011). Very little is known about the role of P2Y2 receptors in osteoclasts.…”

Lack of effect of adenosine on the function of rodent osteoblasts and osteoclasts in vitro

“…Osteoclasts, the bone-resorbing cells also express most P2 receptors [14] and respond to extracellular nucleotides with elevation of intracellular calcium [15]. Moreover, extracellular ATP, ADP and UDP have been shown to increase the formation and resorptive activity of primary rodent osteoclasts in vitro [14,[16][17][18].…”

Does adenosine play a role in bone formation, resorption and repair?

“…Whereas the role of ATP in bone metabolism [1,2] has been revealed to some extent and quite a few papers have been published in this respect, functions of its metabolite adenosine are not understood. Bone remodelling is a continuous, life-long process that maintains skeletal integrity.…”