Jaggedl is essential for osteoblast development during maxillary ossification

摘要

Maxillary hypoplasia occurs due to insufficient maxillary intramembranous ossification, leading to poor dental occlusion, respiratory obstruction and cosmetic deformities. Conditional deletion of Jagged 1 (Jagl) in cranial neural crest (CNC) cells using Wntl-cre;Jaggedlf/f {JaglCKO) led to maxillary hypoplasia characterized by intrinsic differences in bone morphology and density using uCT evaluation JaglCKO maxillas revealed altered collagen deposition, delayed ossification, and reduced expression of early and late determinants of osteoblast development during maxillary ossification. In vitro bone cultures on JaglCKO mouse embryonic maxillary mesen-chymal (MEMM) cells demonstrated decreased mineralization that was also associated with diminished induction of osteoblast determinants. BMP receptor expression was dysregulated in the JaglCKO MEMM cells suggesting that these cells were unable to respond to BMP-induced differentiation. JAGl-Fc rescued in vitro mineralization and osteoblast gene expression changes. These data suggest that JAG1 signaling in CNC-derived MEMM cells is required for osteoblast development and differentiation during maxillary ossification.