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Blood, 15 April 2007, Vol. 109, No. 8, pp. 3253-3259. Prepublished online as a Blood First Edition Paper on December 7, 2006; DOI 10.1182/blood-2006-09-048249.
HEMATOPOIESIS MafB negatively regulates RANKL-mediated osteoclast differentiation1 Research Institute of Medical Sciences and Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju, Korea; 2 Division of Molecular Life Sciences and Center for Cell Signaling Research, Ewha Womans University, Seoul, Korea
Receptor activator of nuclear factor
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| Copyright © 2007 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||||
B ligand (RANKL) induces osteoclast formation from hematopoietic cells via regulation of various transcription factors. Here, we show that MafB negatively regulates RANKL-induced osteoclast differentiation. Expression levels of MafB are significantly reduced by RANKL during osteoclastogenesis. Overexpression of MafB in bone marrow-derived monocyte/macrophage lineage cells (BMMs) inhibits the formation of TRAP+ multinuclear osteoclasts, but phagocytic activity of BMMs is retained. Furthermore, overexpression of MafB in BMMs attenuates the gene induction of NFATc1 and osteoclast-associated receptor (OSCAR) during RANKL-mediated osteoclastogenesis. In addition, MafB proteins interfere with the DNA-binding ability of c-Fos, Mitf, and NFATc1, inhibiting their transactivation of NFATc1 and OSCAR. Furthermore, reduced expression of MafB by RNAi enhances osteoclastogenesis and increases expression of NFATc1 and OSCAR. Taken together, our results suggest that MafB can act as an important modulator of RANKL-mediated osteoclastogenesis. 
