Molecular mechanisms of bone resorption.

This review focuses on osteoclast ontogeny and function, emphasizing three aspects. We describe how a combination of laboratory models available to study the cell plus examination of the osteopetroses, a family of sclerotic diseases of the skeleton, have yielded major insights into osteoclast ontogeny and function. We proceed to describe the cell and molecular machinery enabling osteoclasts to resorb bone. The final, and most speculative, aspect of the review addresses possible mechanisms by which the osteoclast assumes its characteristic morphology, that of a polarized cell on bone. Since little direct information has been forthcoming as to how the osteoclast polarizes, we draw on other polarized cells. In particular, we examine the role of microtubules and members of the small GTPase family, the latter mediating polarized targeting of intracellular vesicles. In the case of the osteoclast, such vesicles probably represent the origin of the highly convoluted ruffled membrane, the cell's characteristic bone resorptive organ.