Normal mineralization and nanostructure of sclerotic bone in mice overexpressing Fra-1

Bone. 2004 May;34(5):776-82. doi: 10.1016/j.bone.2004.01.004.


Increased bone mass due to elevated number of active osteoblasts has been reported for transgenic mice overexpressing the transcription factor Fra-1. To explore the potential of the anabolic action of Fra-1 in treatment of osteoporosis, we examined the integrity of bone matrix generated in Fra-1 transgenic mice. Femora from Fra-1 transgenic (Fra-1 tg) and wild-type littermates were analyzed for bone mineralization density distribution (BMDD) and nanostructure using quantitative backscattered electron imaging (qBEI) and scanning small angle X-ray scattering (scanning-SAXS), respectively. For comparison, we studied mice lacking c-Fos (Fos-/-), which develop osteopetrosis because of the absence of osteoclasts. Morphometrical analysis of metaphyseal spongiosa revealed an up to 5-fold increase in bone volume for Fra-1 transgenic compared to wild type. BMDD indicated a transient lower mineralization of bone for Fra-1 transgenic at 5 and 8 weeks, which became comparable to that of wild-type mice by 8 months. The homogeneity of mineralization was not altered in the Fra-1 transgenic mice at any ages examined. However, it was strikingly reduced in Fos-/- due to an abundance of hypermineralized cartilage. The bone nanostructure did not show abnormalities in Fra-1 transgenic or Fos-/-. These results provide a rationale for the development of therapeutic applications involving Fra-1-induced bone formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone and Bones / anatomy & histology
  • Bone and Bones / ultrastructure*
  • Calcification, Physiologic*
  • Mice
  • Mice, Transgenic
  • Nanotechnology
  • Osteoporosis / physiopathology*
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / physiology*


  • Proto-Oncogene Proteins c-fos
  • fos-related antigen 1