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

Members of the AP-1 family of transcription factors participate in the regu lation of bone cell proliferation and differentiation. We report here a pot ent AP-1-related regulator of osteoblast function: Delta FosB, a naturally occurring truncated form of FosB that arises from alternative splicing of t he fosB transcript and is expressed in osteoblasts. Overexpression of Delta FosB in transgenic mice leads to increased bone formation throughout the s keleton and a continuous post-developmental increase in bone mass, leading to osteosclerosis. In contrast, Delta FosB inhibits adipogenesis both in vi vo and in vitro, and downregulates the expression of early markers of adipo cyte differentiation. Because osteoblasts and adipocytes are thought to sha re a common precursor, it is concluded that Delta FosB transcriptionally re gulates osteoblastogenesis, possibly at the expense of adipogenesis.