Upstream Stimulatory Factors Regulate OSCAR Gene Expression in RANKL-Mediated Osteoclast Differentiation

作者：Kim Jung Ha; Kim Kabsun; Jin Hye Mi; Youn Bang Ung; Song Insun; Choi Hueng Sik; Kim Nacksung^*

来源：Journal of Molecular Biology, 2008, 383(3): 502-511.

DOI：10.1016/j.jmb.2008.08.036

• USF
• gene regulation
• OSCAR
• osteoclast
• RANKL

Receptor activator of nuclear factor kappa B 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 cl in regulating OSCAR gene expression. Taken together, our results indicate that USFs serve as modulators in the induction of OSCAR and RANKL-mediated osteoclastogenesis.

• 出版日期2008-11-14
• 单位河北医科大学