[Frontiers in Bioscience 3, d769-780, August 1, 1998]

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Wayne B. Bowler1, James A. Gallagher and Graeme Bilbe2

1 Human Bone Cell Research Group, Department of Human Anatomy and Cell Biology, University of Liverpool, England, L69 3GE 2 Novartis Pharma A.G., Postfach, K681.4.43, CH-4002 Basel, Switzerland

Received 1/16/98 Accepted 2/17/98


The past five years have seen an explosion in the characterization and cloning of G-protein-coupled receptors expressed by bone cells, this list will inevitably expand, particularly as techniques to isolate and manipulate osteoclasts in vivo evolve. However, it is apparent from those receptors discussed here that G-protein-coupled receptor activation is vital to the functional viability of both osteoblasts and osteoclasts, which in part involves successful communication between cell types. The import of these receptors is further demonstrated in an ability to initiate multiple signals following activation of the same receptor, and their capacity to integrate signals generated following multiple receptor activation. The ability of members of this receptor superfamily to bind and respond to systemic ligands as well those produced locally by the cells of bone, probably facilitates the necessary signaling cross talk required to meet the focal requirements of the remodeling process. The ability of these receptors to so profoundly influence the anabolic or resorptive capacity of bone cells singles them out as potential therapeutic targets in disorders associated with a breakdown in the remodeling process. The selective manipulation of G-protein coupled receptors that target either bone formation or resorption is an exciting possibility for combating skeletal disorders such as osteoporosis, however, as indicated in this review, the complex network of signaling cross talk initiated by these activated receptors remains an obstacle to the development of effective therapeutic regimes.