Normal mineralization and nanostructure of sclerotic bone in mice overexpressing Fra-1.
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.
Roschger
P
P
Ludwig Boltzmann Institute of Osteology and Fourth Med. Department, Hanusch Hospital and UKH Meidling, Vienna, Austria. roschger@ap.univie.ac.at
Matsuo
K
K
Misof
B M
BM
Tesch
W
W
Jochum
W
W
Wagner
E F
EF
Fratzl
P
P
Klaushofer
K
K
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
D016760:Proto-Oncogene Proteins c-fos; D000099169:Fos-Related Antigen 1