Nature Medicine
6, 985 - 990 (2000)
doi:10.1038/79683
Overexpression of  FosB transcription factor(s) increases bone
formation and inhibits adipogenesisG. Sabatakos1, 5, N. A. Sims1, 5, J. Chen2, K. Aoki1, M. B. Kelz2, M. Amling3, Y. Bouali4, K. Mukhopadhyay1, K. Ford1, E. J. Nestler2
& R. Baron11
Departments of Cell Biology and Orthopaedics, Yale
University School of Medicine SHM IE-55, 333 Cedar St,
New Haven, Connecticut, USA, 06520-8044
2
Laboratory of Molecular Psychiatry and Center for Genes
and Behavior Yale University School of Medicine, 34 Park St,
New Haven, Connecticut, USA 06520
3
Department of Trauma Surgery, Hamburg University School
of Medicine Lottestrasse 59, Hamburg
22529, Germany
4
Hoechst Marion Roussel - France, 102
Route de Noisy 93235, Romainville, France
5
G. S. and N. A. S. contributed equally to this study
Correspondence should be addressed to R. Baron roland.baron@yale.eduMembers of the AP-1 family of transcription factors participate in the
regulation of bone cell proliferation and differentiation. We report here
a potent AP-1-related regulator of osteoblast function:  FosB, a naturally
occurring truncated form of FosB that arises from alternative splicing of
the fosB transcript and is expressed in osteoblasts. Overexpression
of FosB in transgenic mice leads to increased bone formation throughout
the skeleton and a continuous post-developmental increase in bone mass, leading
to osteosclerosis. In contrast, FosB inhibits adipogenesis both
in vivo and in vitro, and downregulates the expression of early
markers of adipocyte differentiation. Because osteoblasts and adipocytes are
thought to share a common precursor, it is concluded that FosB transcriptionally
regulates osteoblastogenesis, possibly at the expense of adipogenesis.
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