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Blood, 1 April 2006, Vol. 107, No. 7, pp. 2686-2693. Prepublished online as a Blood First Edition Paper on December 1, 2005; DOI 10.1182/blood-2005-07-2798. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-07-2798v1 107/7/2686    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lee, J. Articles by Kim, N. Search for Related Content PubMed PubMed Citation Articles by Lee, J. Articles by Kim, N. Related Collections Hematopoiesis and Stem Cells Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Id helix-loop-helix proteins negatively regulate TRANCE-mediated osteoclast differentiation Junwon Lee, Kabsun Kim, Jung Ha Kim, Hye Mi Jin, Han Kyung Choi, Seoung-Hoon Lee, Hyun Kook, Kyung Keun Kim, Yoshifumi Yokota, Soo Young Lee, Yongwon Choi, and Nacksung Kim From the Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju, Korea; the Division of Molecular Life Sciences and Center for Cell Signaling Research, Ewha Women's University, Seoul, Korea; the Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia; and the Department of Molecular Genetics, School of Medicine, University of Fukui, Matsuoka, Japan. Tumor necrosis factor (TNF)–related activation-induced cytokine (TRANCE) induces osteoclast formation from monocyte/macrophage lineage cells via various transcription factors, including the Mi transcription factor (Mitf). Here, we show that inhibitors of differentiation/DNA binding (Ids), helix-loop-helix (HLH) transcription factors, negatively regulate TRANCE-induced osteoclast differentiation. Expression levels of Id1, Id2, and Id3 genes are significantly reduced by TRANCE during osteoclastogenesis. Interestingly, overexpression of the 3 Id genes in bone marrow–derived monocyte/macrophage lineage cells (BMMs) inhibits the formation of tartrate-resistant acid phosphatase (TRAP)–positive multinuclear osteoclasts, but it does not alter the ability of BMMs to either phagocytose or differentiate into dendritic cells (DCs). Overexpression of Id2 in BMMs attenuates the gene induction of nuclear factor of activated T cells c1 (NFATc1) and osteoclast-associated receptor (OSCAR) during TRANCE-mediated osteoclastogenesis. Furthermore, Id proteins interact with Mitf, a basic HLH (bHLH) transcription factor, and inhibit its transactivation of OSCAR, which is a costimulatory receptor expressed by osteoclast precursors, by attenuating the DNA binding ability of Mitf to the E-box site of the OSCAR promoter. Taken together, our results reveal both a new facet of negative regulation, mediated by Id proteins, as well as the mechanism whereby TRANCE signaling overcomes it, allowing osteoclastogenesis to proceed. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Kim, S.-H. Lee, J. Ha Kim, Y. Choi, and N. Kim NFATc1 Induces Osteoclast Fusion Via Up-Regulation of Atp6v0d2 and the Dendritic Cell-Specific Transmembrane Protein (DC-STAMP) Mol. Endocrinol., January 1, 2008; 22(1): 176 - 185. [Abstract] [Full Text] [PDF] X. Zhu, Y. Lin, M. Bacanamwo, L. Chang, R. Chai, I. Massud, J. Zhang, M. T. Garcia-Barrio, W. E. Thompson, and Y. E. Chen Interleukin-1 {beta}-induced Id2 gene expression is mediated by Egr-1 in vascular smooth muscle cells Cardiovasc Res, October 1, 2007; 76(1): 141 - 148. [Abstract] [Full Text] [PDF] K. Kim, J. Lee, J. H. Kim, H. M. Jin, B. Zhou, S. Y. Lee, and N. Kim Protein Inhibitor of Activated STAT 3 Modulates Osteoclastogenesis by Down-Regulation of NFATc1 and Osteoclast-Associated Receptor J. Immunol., May 1, 2007; 178(9): 5588 - 5594. [Abstract] [Full Text] [PDF] K. Kim, J. H. Kim, J. Lee, H. M. Jin, H. Kook, K. K. Kim, S. Y. Lee, and N. Kim MafB negatively regulates RANKL-mediated osteoclast differentiation Blood, April 15, 2007; 109(8): 3253 - 3259. [Abstract] [Full Text] [PDF]

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