P2-mediated responses in osteoclasts and osteoclast-like cells

Osteoclasts are multinucleated giant cells of the mononuclear phagocyte lineage that are responsible for bone resorption in vivo. Osteoprotegerin ligand (OPGL) has recently been identified as an important differentiation and activation factor for osteoclasts (Kong et al. [1999] Nature 397:315-323). We and others have demonstrated P2-mediated responses in mononuclear phagocytes and ATP-mediated effects on osteoclasts have also been described (Yu and Ferrier [1994] Cell Signal 6:905-914). The goal of these studies is to identify the role of P2 receptor activation in osteoclast formation and function. In particular, we assessed the role of P2 receptors in intercellular calcium signaling among macrophages and osteoclasts and between osteoblasts and osteoclasts, and studied the role of P2X₇ in OPGL-mediated osteoclast formation. We found that mechanically induced intercellular calcium signaling occurred between osteoblasts and osteoclasts, among J774 macrophage-like cells, and among osteoclasts, but not among bone marrow-derived macrophages. Interestingly, different P2 receptors seemed to be responsible for the propagation of intercellular calcium signals among different cells. In our studies of giant cell formation, we confirmed that expression of P2X₇ enhances giant cell formation in J774 macrophages and in HEK cells. In contrast, RAW cell clones that were selected for resistance to ATP permeabilization were able to form giant cells in response to OPGL, suggesting that the pathways for giant cell and osteoclast may be different.