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Publication : Upstream stimulatory factors regulate OSCAR gene expression in RANKL-mediated osteoclast differentiation.

First Author  Kim JH Year  2008
Journal  J Mol Biol Volume  383
Issue  3 Pages  502-11
PubMed ID  18762192 Mgi Jnum  J:168962
Mgi Id  MGI:4939345 Doi  10.1016/j.jmb.2008.08.036
Citation  Kim JH, et al. (2008) Upstream stimulatory factors regulate OSCAR gene expression in RANKL-mediated osteoclast differentiation. J Mol Biol 383(3):502-11
abstractText  Receptor activator of nuclear factor kappaB ligand (RANKL) induces osteoclast differentiation from hematopoietic precursors via regulation of various transcription factors. Here, we show that upstream stimulatory factors (USFs), which are basic helix-loop-helix leucine zipper transcription factors, are involved in RANKL-mediated osteoclastogenesis and regulation of osteoclast-associated receptor (OSCAR) gene expression, which is an important costimulatory receptor for osteoclast differentiation. USF-1 and USF-2 are expressed in hematopoietic osteoclast precursors and mature osteoclasts. Interestingly, down-regulation of USF-1 by RNA interference or overexpression of a dominant-negative form of USF-1 attenuates osteoclast formation and expression of OSCAR during osteoclastogenesis. Promoter analysis and chromatin immunoprecipitation assays reveal that USFs bind directly to an E-box site in the OSCAR promoter region and activate OSCAR. In addition, USFs interact and cooperate with nuclear factor of activated T cells c1 in regulating OSCAR gene expression. Taken together, our results indicate that USFs serve as modulators in the induction of OSCAR and RANKL-mediated osteoclastogenesis.
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