The osteoclast's bone resorptive cycle. (a) The osteoclast, when unattached to bone, is a non-polarized polykaryon with fibrillar actin (red material) diffusely distributed throughout the cell. (b) Upon attachment to bone the actin cytoskeleton forms a ring, or sealing zone, which isolates the resorptive microenvironment from the general extracellular space. (c) At the same time, acidifying vesicles polarize and insert into the plasma membrane juxtaposed to bone to generate the cell's resorptive organelle, the ruffled membrane. (d) The polarized osteoclast secretes hydrochloric acid (HCL), which acidifies the resorptive microenvironment, leading to mobilization of the mineral phase of bone. The exposed organic matrix is then degraded by cathepsin K (Cath K). Having resorbed the underlying bone to a depth of about 50 μm, the osteoclast detaches, disassembles its actin ring and ruffled membrane, and migrates to its next site of resorption.