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| Subject Categories: Cell & Tissue Architecture | Molecular Biology of Disease |
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| The EMBO Journal
(2004) 23, 2789–2799, doi:10.1038/sj.emboj.7600282 Published online 1 July 2004 |
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| The Fos-related antigen Fra-1 is an activator of bone matrix formation |
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| Robert Eferl1, Astrid Hoebertz1, Arndt F Schilling2, Martina Rath1, Florian Karreth1, Lukas Kenner1, Michael Amling2 and Erwin F Wagner1 |
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1 Research Institute of Molecular Pathology (IMP), Vienna, Austria 2 Department of Trauma, Hand and Reconstructive Surgery, Hamburg, University School of Medicine, Hamburg, Germany To whom correspondence should be addressed Erwin F Wagner, Research Institute of Molecular Pathology (IMP), Dr Bohr-Gasse 7, 1030 Vienna, Austria. Tel.: +43 1 79730; Fax: +43 1 7989390; E-mail: wagner@imp.univie.ac.at Received 9 March 2004; Accepted 28 May 2004; Published online 1 July 2004. |
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| Abstract |
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Ectopic expression of the transcription factor Fra-1 in transgenic mice leads to osteosclerosis, a bone disorder characterized by increased bone mass. The molecular basis for this phenotype is unknown and Fra-1 functions cannot be studied by a conventional loss-of-function approach, since fra-1-knockout mice die in utero likely due to placental defects. Here we show that the lethality of fra-1-knockout mice can be rescued by specific deletion of Fra-1 only in the mouse embryo and not in the placenta. Mice lacking Fra-1 (fra-1 /) are viable and develop osteopenia, a low bone mass disease. Long bones of fra-1/ mice appear to have normal osteoclasts but express reduced amounts of bone matrix components produced by osteoblasts and chondrocytes such as osteocalcin, collagen1a2 and matrix Gla protein. The gene for matrix Gla protein seems to be a specific target of Fra-1 since its expression was markedly increased in the long bones of fra-1-transgenic mice. These results uncover a novel function of Fra-1 in regulating bone mass through bone matrix production by osteoblasts and chondrocytes. |
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| Keywords: AP-1, bone extracellular matrix, conditional Fra-1 knockout, osteoblasts, osteopenia |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSHow many factors are required to remodel bone? Nature Medicine News and Views (01 Sep 2000) Nature Medicine News and Views (01 Nov 1995) RESEARCHOverexpression of ΔFosB transcription factor(s) increases bone formation and inhibits adipogenesis Nature Medicine Article (01 Sep 2000) Osteoclast size is controlled by Fra-2 through LIF/LIF-receptor signalling and hypoxia Nature Letters to Editor (10 Jul 2008) |
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