MafB negatively regulates RANKL-mediated osteoclast differentiation - PubMed (original) (raw)

. 2007 Apr 15;109(8):3253-9.

doi: 10.1182/blood-2006-09-048249. Epub 2006 Dec 7.

Affiliations

Free article

MafB negatively regulates RANKL-mediated osteoclast differentiation

Kabsun Kim et al. Blood. 2007.

Free article

Abstract

Receptor activator of nuclear factor kappaB 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.

PubMed Disclaimer

Similar articles

Cited by

Publication types

MeSH terms

Substances

LinkOut - more resources