Osteoblasts are large multinucleated bone-resorbing cells formed by the fusion of monocyte/macrophage-derived precursors, and they are believed to undergo apoptosis when bone resorption is complete. In a recent study, Michelle M. McDonald et al. developed a minimally invasive system for longitudinal real-time imaging of cellular dynamics in the tibia of mice.
By intravital imaging, they revealed that RANKL-stimulated osteoclasts have an alternative cell fate in which they fission into daughter cells called osteomorphs. Osteomorphs are smaller, more motile daughter cells that retain the ability to fuse to form functional osteoclasts. In contrast to osteoclasts that are attached to bone, osteomorphs are found in the bone marrow and blood. Single-cell RNA sequencing showed that osteomorphs are transcriptionally distinct from osteoclasts and macrophages and express a number of non-canonical osteoclast genes that are associated with structural and functional bone phenotypes when deleted in mice. Furthermore, genetic variation in human orthologs of osteomorph genes causes monogenic skeletal disorders and associates with bone mineral density, a polygenetic skeletal trait.
A consequence of osteoclast recycling is that it allows a committed pool of cells to be maintained during periods of inactivity that are primed to respond rapidly to changing conditions. The authors concluded that osteoclast recycling not only provides a paradigm for understanding the behavior and fate of these cells in their physiological niche in vivo but also a framework for understanding skeletal diseases associated with dysregulated bone resorption and the effects of drugs used to treat them.