TY - JOUR
T1 - A mouse model for human osteogenesis imperfecta type VI
AU - Bogan, Rosalind
AU - Riddle, Ryan C.
AU - Li, Zhu
AU - Kumar, Sarvesh
AU - Nandal, Anjali
AU - Faugere, Marie Claude
AU - Boskey, Adele
AU - Crawford, Susan E.
AU - Clemens, Thomas L.
PY - 2013/7
Y1 - 2013/7
N2 - 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.
AB - 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.
KW - BONE MINERALIZATION
KW - OSTEOBLAST
KW - OSTEOGENESIS IMPERFECTA
KW - PEDF
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U2 - 10.1002/jbmr.1892
DO - 10.1002/jbmr.1892
M3 - Article
C2 - 23413146
AN - SCOPUS:84879215697
SN - 0884-0431
VL - 28
SP - 1531
EP - 1536
JO - Journal of Bone and Mineral Research
JF - Journal of Bone and Mineral Research
IS - 7
ER -