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

Nature Medicine volume 6, pages 980–984 (2000)Cite this article

An Erratum to this article was published on 01 December 2000

Abstract

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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Figure 1: Generation of fra-1 transgenic mice.
Figure 2: Radiological and histological analysis.
Figure 3: In vivo analysis of bone formation of fra-1 transgenic mice.
Figure 4: Analysis of fra-1 transgenic osteoblasts and osteoclasts in vitro.
Figure 5: Molecular analysis of fra-1 transgenic osteoblasts.

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Acknowledgements

We thank K. Kratochwil for his generous help with kidney capsule transplantation experiments, and D. Lallemand, M. Yaniv and G. Karsenty for providing antibodies. We also thank G. Christofori, A. Grigoriadis and M. Cotten for critical reading of the manuscript. This work was supported by a Marie-Curie-Fellowship from the European Community to W.J. (ERBFMBICT961780) and a TMR postdoctoral stipend to J.P.D. (ERBFMRX CT960044). This work was partially supported by the Austrian Science Foundation (S07406-MOB) and the Austrian Industrial Research Promotion Fund.

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  1. Wolfram Jochum

    Present address: Institute of Clinical Pathology, University Hospital, Schmelzbergstrasse 12, CH-8091, Zürich, Switzerland

Authors and Affiliations

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

    Wolfram Jochum, Jean-Pierre David, Candace Elliott, Anton Wutz, Koichi Matsuo & Erwin F. Wagner

  2. Institute for Histology and Embryology, Bone and Biomaterials Research, University of Vienna, Schwarzspanierstrasse 17, Vienna, A-1090, Austria

    Hanns Plenk Jr.

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  1. Wolfram Jochum
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Correspondence to Erwin F. Wagner.

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Jochum, W., David, JP., Elliott, C. et al. Increased bone formation and osteosclerosis in mice overexpressing the transcription factor Fra-1. Nat Med 6, 980–984 (2000). https://doi.org/10.1038/79676

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