RANK, the primary regulator of osteoclastogenesis, mediates the effects of denosumab, an anti-RANKL antibody that provides antiresorptive therapy to millions of people affected by conditions such as osteoporosis. The drug typically reduces bone formation by inhibiting bone remodeling, but has occasionally been observed to paradoxically maintain or increase bone formation in patients. The Kwon lab has identified RANK as an osteoblastic marker in developing zebrafish, providing an opportunity to further investigate the mechanism by which RANK signaling acts in the osteoblast lineage. Zebrafish, and other evolutionary distant species, may provide insight into the ancestral roles of RANK in mammalian bone development. Through the utilization of single-cell RNA sequencing, Tia Schlosser will investigate the evolution of osteoblasts and RANK across species to advance the understanding of RANK/RANKL signaling in human bone.
