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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 14, 2005 Accepted November 22, 2005 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* Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju, Korea, Republic of Division of Molecular Life Sciences and Center for Cell Signaling Research, Ewha Womans University, Seoul, Korea, Republic of Abramson Family Cancer Research Institute, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA Department of Molecular Genetics, School of Medicine, University of Fukui, Matsuoka, Fukui, Japan * Corresponding author; email: nacksung{at}jnu.ac.kr. Tumor necrosis factor (TNF)-related activation-induced cytokine (TRANCE) induces osteoclast formation from monocyte/macrophage lineage cells via various transcription factors, including microphthalmia 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 Id-1, Id-2, and Id-3 genes are significantly reduced by TRANCE during osteoclastogenesis. Interestingly, overexpression of the three Id genes in bone marrow-derived monocyte/macrophage lineage cells (BMMs) inhibits the formation of 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 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 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: H. C. Suh, M. Ji, J. Gooya, M. Lee, K. D. Klarmann, and J. R. Keller Cell-nonautonomous function of Id1 in the hematopoietic progenitor cell niche Blood, August 6, 2009; 114(6): 1186 - 1195. [Abstract] [Full Text] [PDF] J. H. Kim, H. M. Jin, K. Kim, I. Song, B. U. Youn, K. Matsuo, and N. Kim The Mechanism of Osteoclast Differentiation Induced by IL-1 J. Immunol., August 1, 2009; 183(3): 1862 - 1870. [Abstract] [Full Text] [PDF] T. Kim, K. Kim, S. H. Lee, H.-S. So, J. Lee, N. Kim, and Y. Choi Identification of LRRc17 as a Negative Regulator of Receptor Activator of NF-{kappa}B Ligand (RANKL)-induced Osteoclast Differentiation J. Biol. Chem., May 29, 2009; 284(22): 15308 - 15316. [Abstract] [Full Text] [PDF] 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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