Osteoclasts, Master Sculptors of Bone

Osteoclasts are multinucleated cells with the unique ability to resorb bone matrix. Excessive production or activation of osteoclasts leads to skeletal pathologies that affect a significant portion of the population. Although therapies that effectively target osteoclasts have been developed, they are associated with sometimes severe side effects, and a fuller understanding of osteoclast biology may lead to more specific treatments. Along those lines, a rich body of work has defined essential signaling pathways required for osteoclast formation, function, and survival. Nonetheless, recent studies have cast new light on long-held views regarding the origin of these cells during development and homeostasis, their life span, and the cellular sources of factors that drive their production and activity during homeostasis and disease. In this review, we discuss these new findings in the context of existing work and highlight areas of ongoing and future investigation.