title: MafB negatively regulates RANKL-mediated osteoclast differentiation.
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.
authors.affiliation: Research Institute of Medical Sciences and Medical Research Center for Gene Regulation, Chonnam National University Medical School, Hak-Dong 5, Dong-Ku, Gwangju 501-746, Korea.
authors.forename: Kabsun
authors.initials: K
authors.lastname: Kim
authors.forename: Jung Ha
authors.initials: JH
authors.lastname: Kim
authors.forename: Junwon
authors.initials: J
authors.lastname: Lee
authors.forename: Hye Mi
authors.initials: HM
authors.lastname: Jin
authors.forename: Hyun
authors.initials: H
authors.lastname: Kook
authors.forename: Kyung Keun
authors.initials: KK
authors.lastname: Kim
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Nacksung
authors.initials: N
authors.lastname: Kim
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000235:genetics; D015726:Giant Cells / Q000166:cytology / Q000378:metabolism; D006412:Hematopoietic Stem Cells; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D051258:MafB Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D050778:NFATC Transcription Factors / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D053245:RANK Ligand / Q000096:biosynthesis* / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D011956:Receptors, Cell Surface / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D051258:MafB Transcription Factor; C490406:Mafb protein, mouse; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; C450519:Oscar protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D053245:RANK Ligand; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; C505689:Tnfsf11 protein, mouse