Endocrine Abstracts

Bone is a dynamic tissue, maintained and repaired by the actions of, osteoclasts, osteoblasts and osteocytes, together with a variety of bone marrow cells, stromal cells and endothelium. Osteoblasts lay down bone and this is subsequently remodelled by osteoclasts. Osteocytes act mainly as mechanosensors. Osteoclasts are of haemopoietic origin, whereas osteoblasts are derived from mesenchymal stem cells. During cell differentiation and in mature cells, cell adhesion molecules are important regulators of osteoclast function, allowing adhesion, migration, transmigration through endothelium and they act as true signalling molecules. Osteoclasts express mainly members of the integrin family of cell-matrix adhesion receptors. They express very high numbers of vitronectin receptors (VNR, αvβ3and in immature cells αvβ5). This receptor can, at least in vitro, bind to a wide range of RGD-containing bone matrix proteins, but the true in vivo ligand for the receptor has not been identified. VNR is expressed on the plasma membrane. In polarised, bone resorbing osteoclasts, VNR is mainly concentrated on the basolateral membrane and in the ruffled border, areas not in direct contact with the bone surface, suggesting that it has a role beyond facilitating initial cell adhesion. Osteoclasts also express high levels of α2β1 integrins, which facilitate adhesion to collagen and express αvβ1, which can bind fibronectin. Expression of cadherins is limited, with possibly a role for E-cadherin during cell development. ICAM-1 and V-CAM have been found to be involved in osteoclast development in functional studies, but this is most likely through expression on osteoblasts and interactions with LFA-1 on osteoclast precursors. CD44 is expressed on osteoclast and may allow adhesion to osteopontin and hyaluronan in vivo. No major adhesion molecule defects have been found in osteoclast diseases so far, and, surprisingly, gene knockout studies of β3 integrins have not yielded very dramatic bone phenotypes, likely through compensation by β1 integrins. Even so, the high expression level of VNR and its clear importance in osteoclast function has made this a target for therapies aimed at reducing bone resorption.