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BioMed Research International
Volume 2013 (2013), Article ID 292506, 11 pages
http://dx.doi.org/10.1155/2013/292506
Research Article

Craniosynostosis-Associated Fgfr2C342Y Mutant Bone Marrow Stromal Cells Exhibit Cell Autonomous Abnormalities in Osteoblast Differentiation and Bone Formation

1Department of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Michigan, Ann Arbor, MI 48109-1078, USA
2Department of Oral and Maxillofacial Surgery, School of Dentistry, Kyungpook National University, Jung Gu, Daegu, Republic of Korea

Received 11 January 2013; Revised 18 March 2013; Accepted 29 March 2013

Academic Editor: Zhao Lin

Copyright © 2013 J. Liu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

We recently reported that cranial bones of 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 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. 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 mice also formed less bone when allowed to differentiate in a 3D matrix in vivo. Cortical bone parameters were diminished in long bones of mice. These results demonstrate that marrow stromal cells of mice have an autonomous defect in osteoblast differentiation and bone mineralization, and that the mutation influences both the axial and appendicular skeletons.