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Increased bone formation and osteosclerosis in mice overexpressing the transcription factor Fra-1.

Bone formation by osteoblasts is essential for skeletal growth and remodeling. Fra-1 is a c-Fos-related protein belonging to the AP-1 family of transcription factors. Here we show that transgenic mice overexpressing Fra-1 in various organs develop a progressive increase in bone mass leading to osteosclerosis of the entire skeleton, which is due to a cell-autonomous increase in the number of mature osteoblasts. Moreover, osteoblast differentiation, but not proliferation, was enhanced and osteoclastogenesis was also elevated in vitro. These data indicate that, unlike c-Fos, which causes osteosarcomas, Fra-1 specifically enhances bone formation, which may be exploited to stimulate bone formation in pathological conditions.

Pubmed ID: 10973316


  • Jochum W
  • David JP
  • Elliott C
  • Wutz A
  • Plenk H
  • Matsuo K
  • Wagner EF


Nature medicine

Publication Data

September 6, 2000

Associated Grants


Mesh Terms

  • Animals
  • Calcinosis
  • Cell Differentiation
  • Mice
  • Mice, Transgenic
  • Osteoblasts
  • Osteosclerosis
  • Phenotype
  • Proto-Oncogene Proteins c-fos