NF-κB ligand (RANKL; also called tumor necrosis factor-related activation-induced cytokine (TRANCE), osteoprotegerin ligand (OPGL) or osteoclast differentiation factor (ODF)) macrophage colony-stimulating factor (M-CSF) or granulocyte-macrophage colony-stimulating factor (GM-

Bone resorption is necessary for many skeletal processes. It is an obligatory event during bone growth, tooth eruption and fracture healing, and is also necessary for the maintenance of an appropriate level of blood calcium. In the adult human skeleton, continuous physiological remodelling of bone is exclusively dependent on bone resorption. In several human diseases (e.g. malignant hypercalcemia and postmenopausal osteoporosis) enhanced bone resorption is the key pathophysiological event, and therapies for these diseases are currently based on its inhibition. In contrast, some rare genetic disorders are manifested as decreased resorption and lead to osteopetrosis. Osteoclasts are multinuclear cells derived from hematopoietic stem cells (Suda et al., 1992). Their differentiation pathway is common to that of macrophages and dendritic cells. Thus a promyeloid precursor can differentiate into either an osteoclast, a macrophage or a dendritic cell, depending on whether it is exposed to receptor activator of NF-κB ligand (RANKL; also called tumor necrosis factor-related activation-induced cytokine (TRANCE), osteoprotegerin ligand (OPGL) or osteoclast differentiation factor (ODF)) macrophage colony-stimulating factor (M-CSF) or granulocyte-macrophage colony-stimulating factor (GMCSF), respectively (Kong et al., 1999; Nutt et al., 1999; Rolink et al., 1999; Suda et al., 1999). Simonet et al. (1997) found that several cells and tissues produce a soluble factor, osteoprotegerin (OPG), that strongly inhibits osteoclast formation in vitro and in vivo. More recently, several groups demonstrated that bone marrow stromal cells and osteoblasts produce membrane bound and soluble RANKL/TRANCE/OPGL/ODF, an important positive regulator of osteoclast formation (Lacey et al., 1998). The inhibitory effect of OPG on the osteoclast differentiation is due to the fact that it can prevent the binding of RANKL to its receptor, RANK (Hsu et al., 1999). Major breakthroughs in osteoclast differentiation have thus been made, and some excellent reviews on this topic has been written recently (Suda et al., 1999; Roodman, 1999). Here, we do not discuss any further details of the osteoclast differentiation and its regulation but encourage readers to familiarise themselves with the above-mentioned articles. Osteoclasts have developed efficient and unique machinery for dissolving mineral and degrading organic bone matrix. Our understanding of the cellular and molecular processes that are utilized by these professional hard-tissue destroyers has also significantly increased during the past decade. Here, we discuss the recent progress in the understanding of the cell biology of osteoclasts function and activation. Furthermore, we suggest that these cells represent good model systems for addressing some general questions in cell biology. 377 Journal of Cell Science 113, 377-381 (2000) Printed in Great Britain © The Company of Biologists Limited 2000 JCS1073