Craniosynostosis-associated Fgfr2(C342Y) mutant bone marrow stromal cells exhibit cell autonomous abnormalities in osteoblast differentiation and bone formation.

ABSTRACT: We recently reported that cranial bones of Fgfr2(C342Y/+) craniosynostotic mice are diminished in density when compared to those of wild type mice, and that cranial bone cells isolated from the mutant mice exhibit inhibited late stage osteoblast differentiation. To provide further support for the idea that craniosynostosis-associated Fgfr mutations lead to cell autonomous defects in osteoblast differentiation and mineralized tissue formation, here we tested bone marrow stromal cells isolated from Fgfr2(C342Y/+) mice for their ability to differentiate into osteoblasts. Additionally, to determine if the low bone mass phenotype of Crouzon syndrome includes the appendicular skeleton, long bones were assessed by micro CT. Fgfr2(C342Y/+) cells showed increased osteoblastic gene expression during early osteoblastic differentiation but decreased expression of alkaline phosphatase mRNA and enzyme activity, and decreased mineralization during later stages of differentiation, when cultured under 2D in vitro conditions. Cells isolated from Fgfr2(C342Y/+) mice also formed less bone when allowed to differentiate in a 3D matrix in vivo. Cortical bone parameters were diminished in long bones of Fgfr2(C342Y/+) mice. These results demonstrate that marrow stromal cells of Fgfr2(C342Y/+) mice have an autonomous defect in osteoblast differentiation and bone mineralization, and that the Fgfr2(C342Y) mutation influences both the axial and appendicular skeletons.

SUBMITTER: Liu J 

PROVIDER: S-EPMC3665166 | biostudies-other | 2013

REPOSITORIES: biostudies-other