In this study, we postulate that (1) JAG1 can induce osteoblast differentiation and mineralization of pediatric human bone-derived osteoblast-like (HBO) cells, and (2) the delivery of JAG1 non-canonical signaling constitutes an effective treatment for inducing bone regeneration in a pediatric, preclinical CF bone loss model. Here, JAG1 is linked to cystic fibrosis.