title: Normal mineralization and nanostructure of sclerotic bone in mice overexpressing Fra-1.
abstract: 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.
authors.affiliation: Ludwig Boltzmann Institute of Osteology and Fourth Med. Department, Hanusch Hospital and UKH Meidling, Vienna, Austria. roschger@ap.univie.ac.at
authors.forename: P
authors.initials: P
authors.lastname: Roschger
authors.forename: K
authors.initials: K
authors.lastname: Matsuo
authors.forename: B M
authors.initials: BM
authors.lastname: Misof
authors.forename: W
authors.initials: W
authors.lastname: Tesch
authors.forename: W
authors.initials: W
authors.lastname: Jochum
authors.forename: E F
authors.initials: EF
authors.lastname: Wagner
authors.forename: P
authors.initials: P
authors.lastname: Fratzl
authors.forename: K
authors.initials: K
authors.lastname: Klaushofer
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000033:anatomy & histology / Q000648:ultrastructure*; D002113:Calcification, Physiologic; D051379:Mice; D008822:Mice, Transgenic; D036103:Nanotechnology; D010024:Osteoporosis / Q000503:physiopathology*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000502:physiology*; D000099169:Fos-Related Antigen 1
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D000099169:Fos-Related Antigen 1