Overexpression of ΔFosB transcription factor(s) increases bone formation and inhibits adipogenesis

G. Sabatakos, N. A. Sims, J. Chen, K. Aoki, M. B. Kelz, M. Amling, Y. Bouali, K. Mukhopadhyay, K. Ford, E. J. Nestler, R. Baron

Research output: Contribution to journalArticlepeer-review

299 Scopus citations

Abstract

Members 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: ΔFosB, a naturally occurring truncated form of FosB that arises from alternative splicing of the fosB transcript and is expressed in osteoblasts. Overexpression of ΔFosB 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, ΔFosB 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 ΔFosB transcriptionally regulates osteoblastogenesis, possibly at the expense of adipogenesis.

Original languageEnglish
Pages (from-to)985-990
Number of pages6
JournalNature Medicine
Volume6
Issue number9
DOIs
StatePublished - Sep 2000
Externally publishedYes

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