A mouse model for human osteogenesis imperfecta type VI

Rosalind Bogan, Ryan C. Riddle, Zhu Li, Sarvesh Kumar, Anjali Nandal, Marie Claude Faugere, Adele Boskey, Susan E. Crawford, Thomas L. Clemens

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1531-1536
Number of pages6
JournalJournal of Bone and Mineral Research
Volume28
Issue number7
DOIs
StatePublished - Jul 2013

Keywords

  • BONE MINERALIZATION
  • OSTEOBLAST
  • OSTEOGENESIS IMPERFECTA
  • PEDF

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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