Upstream stimulatory factors regulate OSCAR gene expression in RANKL-mediated osteoclast differentiation.
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.
Kim
Jung Ha
JH
National Research Laboratory for Regulation of Bone Metabolism and Disease, Research Institute Medical Sciences, Chonnam National University Medical School, Dong-Ku, Gwangju 501-746, Korea.
Kim
Kabsun
K
Jin
Hye Mi
HM
Youn
Bang Ung
BU
Song
Insun
I
Choi
Hueng-Sik
HS
Kim
Nacksung
N