P2-mediated responses in osteoclasts and osteoclast-like cells

Osteoclasts are multinucleated giant cells of the mononuclear phagocyte lin eage that are responsible for bone resorption in vivo. Osteoprotegerin liga nd (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 phago cytes 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 fun ction. In particular, we assessed the role of P2 receptors in intercellular calcium signaling among macrophages and osteoclasts and between osteoblast s and osteoclasts, and studied the role of P2X(7) in OPGL-mediated osteocla st formation. We found that mechanically induced intercellular calcium sign aling occurred between osteoblasts and osteoclasts, among J774 macrophage-l ike cells, and among osteoclasts, but not among bone marrow-derived macroph ages. interestingly, different P2 receptors seemed to be responsible for th e propagation of intercellular calcium signals among different cells. In ou r studies of giant cell formation, we confirmed that expression of P2X7 enh ances giant cell formation in J774 macrophages and in HEK cells. In contras t, RAW cell clones that were selected for resistance to ATP permeabilizatio n were able to form giant cells in response to OPGL, suggesting that the pa thways for giant cell and osteoclast may be different. (C) 2001 Wiley-Liss, Inc.