Osteoclast motility: putting the brakes on bone resorption.

As the skeleton ages, the balanced formation and resorption of normal bone remodeling is lost, and bone loss predominates. The osteoclast is the specialized cell that is responsible for bone resorption. It is a highly polarized cell that must adhere to the bone surface and migrate along it while resorbing, and cytoskeletal reorganization is critical. Podosomes, highly dynamic actin structures, mediate osteoclast motility. Resorbing osteoclasts form a related actin complex, the sealing zone, which provides the boundary for the resorptive microenvironment. Similar to podosomes, the sealing zone rearranges itself to allow continuous resorption while the cell is moving. The major adhesive protein controlling the cytoskeleton is αvβ3 integrin, which collaborates with the growth factor M-CSF and the ITAM receptor DAP12. In this review, we discuss the signaling complexes assembled by these molecules at the membrane, and their downstream mediators that control OC motility and function via the cytoskeleton.