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Nat Med. 2000 Sep;6(9):980-4.

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

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Research Institute of Molecular Pathology (I.M.P.), Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.

Erratum in

  • Nat Med 2000 Dec;6(12):1412.


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.

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