MafB negatively regulates RANKL-mediated osteoclast differentiation.
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.
Kim
Kabsun
K
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.
Kim
Jung Ha
JH
Lee
Junwon
J
Jin
Hye Mi
HM
Kook
Hyun
H
Kim
Kyung Keun
KK
Lee
Soo Young
SY
Kim
Nacksung
N
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
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