A Mouse Model for Human Osteogenesis Imperfecta Type VI. (18th June 2013)

• Record Type: Journal Article
• Authors: Bogan, Rosalind; Riddle, Ryan C; Li, Zhu; Kumar, Sarvesh; Nandal, Anjali; Faugere, Marie‐Claude; Boskey, Adele; Crawford, Susan E; Clemens, Thomas L
• Is Part Of: Journal of bone and mineral research. Volume 28:Number 7(2013:Jul.)
• Page Start: 1531
• Page End: 1536
• Publication Date: 2013-06-18
• Subjects: Bones -- Metabolism -- Periodicals; Mineral metabolism -- Periodicals; 612.392
• DOI: 10.1002/jbmr.1892
• Languages: English
• ISSNs: 0884-0431

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>ABSTRACT</title> <sec id="jbmr1892-sec-0001" sec-type="section"> <p>Osteogenesis imperfecta type VI (OI type VI) has recently be linked to a mutation in the <italic>SERPINF1</italic> gene, which encodes pigment epithelium‐derived factor (PEDF), a ubiquitously expressed protein originally described for its neurotrophic and antiangiogenic properties. In this study, we characterized the skeletal phenotype of a mouse with targeted disruption of <italic>Pedf</italic>. In normal mouse bone, Pedf was localized to osteoblasts and osteocytes. Micro–computed tomography (µCT) and quantitative bone histomorphometry in femurs of mature Pedf null mutants revealed reduced trabecular bone volume and the accumulation of unmineralized bone matrix. Fourier transform infrared microscopy (FTIR) indicated an increased mineral:matrix ratio in mutant bones, which were more brittle than controls. In vitro, osteoblasts from Pedf null mice exhibited enhanced mineral deposition as assessed by Alizarin Red staining and an increased mineral:matrix determined by FTIR analysis of calcified nodules. The findings in this mouse model mimic the principal structural and biochemical features of bone observed in humans with OI type VI and consequently provide a useful model with which to further investigate the role of PEDF in this bone disorder.</p> </sec> </abstract>