Students of the Bone Eaters: An Exploration of Osteoclast Multinucleation

Abstract Purpose of Review Here, we explore how the osteoclast’s many nuclei inform behavior, set activity, and underpin osteoclast-driven pathologies. Recent Findings Over the last decade, new discoveries have demonstrated that osteoclast multinucleation is a major determinant of activity and driver of pathologic behavior. We open with a review of postnatal skeletal maintenance and the role osteoclasts play in coordinating the multicellular unit responsible for life-long skeletal development. Then, we focus the second half on recent developments in the understanding of how multinucleation influences osteoclast resorptive behavior, underpins skeletal pathology, and close with a discussion on the fate and nature of these syncytial cells. Much of this latter discussion is stimulated by recent observations focusing on the behavior and fate of individual osteoclasts as compared to previous systemic measurements of their activity. Summary In the end, work over the last decade - in particular, fate tracing, advances in the live imaging of osteoclast activity, and mechanistic observations of syncytial fission - pushes us to consider the possibility that osteoclasts are more than individual cells but instead operate as community of individuals held in a common boarder. It seems to us that Evolution, when faced with a task too great for one, answered with many - A Syncytial Community.