A Mouse Model for Human Osteogenesis Imperfecta Type VI

ABSTRACT Osteogenesis imperfecta type VI (OI type VI) has recently be linked to a mutation in the SERPINF1 gene, which encodes pigment epithelium‐derived factor (PEDF), a ubiquitously expressed protein originally described for its neurotrophic and antiangiogenic properties. In this study, we charact...

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Bibliographic Details
Published in:Journal of bone and mineral research 2013-07, Vol.28 (7), p.1531-1536
Main Authors: Bogan, Rosalind, Riddle, Ryan C, Li, Zhu, Kumar, Sarvesh, Nandal, Anjali, Faugere, Marie‐Claude, Boskey, Adele, Crawford, Susan E, Clemens, Thomas L
Format: Article
Language:English
Subjects:
Animals
Bone Density - genetics
BONE MINERALIZATION
Disease Models, Animal
Eye Proteins - genetics
Eye Proteins - metabolism
Femur - diagnostic imaging
Femur - metabolism
Humans
Mice
Mice, Mutant Strains
Nerve Growth Factors - genetics
Nerve Growth Factors - metabolism
OSTEOBLAST
Osteocytes - metabolism
Osteocytes - pathology
OSTEOGENESIS IMPERFECTA
Osteogenesis Imperfecta - diagnostic imaging
Osteogenesis Imperfecta - genetics
Osteogenesis Imperfecta - metabolism
PEDF
Radiography
Serpins - genetics
Serpins - metabolism
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Summary:ABSTRACT Osteogenesis imperfecta type VI (OI type VI) has recently be linked to a mutation in the SERPINF1 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 Pedf. 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.
ISSN:0884-0431
1523-4681
DOI:10.1002/jbmr.1892