Distinctive subdomains in the resorbing surface of osteoclasts.

We employed a novel technique to inspect the substrate-apposed surface of activated osteoclasts, the cells that resorb bone, in the scanning electron microscope. The surface revealed unexpected complexity. At the periphery of the cells were circles and crescents of individual or confluent nodules.

Bone is not essential for osteoclast activation.

Background: The mechanism whereby bone activates resorptive behavior in osteoclasts, the cells that resorb bone, is unknown. It is known that α(v)β(3) ligands are important, because blockade of α(v)β(3) receptor signaling inhibits bone resorption, but this might be through inhibition of adhesion or migration rather than resorption itself. Nor is it known whether α(v)β(3) ligands are sufficient for resorption the consensus is that bone mineral is essential for the recognition of bone as the substrate appropriate for resorption.

The resorptive apparatus of osteoclasts supports lysosomotropism and increases potency of basic versus non-basic inhibitors of cathepsin K.

In mice and humans, the effect of genetic deficiency of cathepsin K (catK) is impaired bone resorption, or osteopetrosis. Inhibition of catK is therefore a promising strategy for the treatment of osteoporosis. The enzyme acts in an acid environment.