title: 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 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.
authors: Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: Rosalind
authors: R
authors: Bogan
authors: Ryan C
authors: RC
authors: Riddle
authors: Zhu
authors: Z
authors: Li
authors: Sarvesh
authors: S
authors: Kumar
authors: Anjali
authors: A
authors: Nandal
authors: Marie-Claude
authors: MC
authors: Faugere
authors: Adele
authors: A
authors: Boskey
authors: Susan E
authors: SE
authors: Crawford
authors: Thomas L
authors: TL
authors: Clemens
mesh_terms: D000818:Animals; D015519:Bone Density / Q000235:genetics*; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D005269:Femur / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D009414:Nerve Growth Factors / Q000235:genetics* / Q000378:metabolism; D010011:Osteocytes / Q000378:metabolism / Q000473:pathology; D010013:Osteogenesis Imperfecta / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism; D011859:Radiography; D015843:Serpins / Q000235:genetics* / Q000378:metabolism; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor