The P2X7 Receptor: A Key Player in Immune-Mediated Bone Loss?

Figure 1

The physiological functions of the P2X7 receptor in bone cells. Numbers in brackets refer to published cellular functions associated with P2X7 receptor activation and/or expression. (1) Mechanostimulation induces ATP release. (2) Modulation of ATP release by the P2X7 receptor. ATP release from osteoblasts involves vesicular exocytosis. In osteoclasts, ATP release is associated with P2X7 activation, but the exact mechanism has not yet been determined. (3) Osteoblasts may be a source of local cytokine release possibly through the P2X7 inflammasome pathway. (4) ATP is released from osteoblasts upon mechanical and nucleotide stimulation and mediates paracrine signalling to neighboring cells via P2X7 receptor activation. (5) P2X7 receptor activation induces RANKL expression in osteoblasts and subsequently formation of osteoclasts from mononuclear precursors. (6) P2X7 receptors activation is coupled to intracellular signalling pathways in osteoblasts that induce cell growth and bone formation. (7) In osteoclasts, P2X7 receptor activation is linked to fusion of mononuclear osteoclast precursors and to apoptosis and cell survival hand to activation of osteoclastic bone resorption.