| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Research Institute of Medical Sciences and Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju, Korea;
Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232; and
Division of Molecular Life Science and Center for Cell Signaling Research, Ewha Woman University, Seoul, Korea
Protein inhibitor of activated STAT3 (PIAS3) has been shown to regulate the activity of various transcription factors. In this study, we show that the overexpression of PIAS3 in bone marrow-derived monocyte/macrophage lineage cells attenuates osteoclast formation and down-regulates the expression of NFATc1 and osteoclast-associated receptor (OSCAR), which are important modulators in osteoclastogenesis. PIAS3 has been shown to associate with histone deacetylase 1 as well as with transcription factors, including the microphthalmia transcription factor, NFATc1, and c-Fos. Moreover, overexpression of PIAS3 inhibits the transactivation of target genes such as NFATc1 and OSCAR. This inhibitory effect of PIAS3 is possibly mediated by histone deacetylase 1 recruitment to the promoter regions of NFATc1 and OSCAR. Furthermore, silencing of PIAS3 by RNA interference in osteoclast precursors enhances osteoclast formation as well as gene expression of NFATc1 and OSCAR. Taken together, our results reveal that PIAS3 acts as a modulator in osteoclastogenesis.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by Korea Research Foundation Grant KRF-2005-015-E00152 and Grant R13-2002-013-03001-0 from the Korea Science and Engineering Foundation through the Medical Research Center for Gene Regulation at Chonnam National University.
2 K.K. and J.L. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Nacksung Kim, Medical Research Center for Gene Regulation, Chonnam National University Medical School, Hak-Dong 5, Dong-Ku, Gwangju, Korea. E-mail address: nacksung{at}jnu.ac.kr
4 Abbreviations used in this paper: RANKL, receptor activator of nuclear factor 
B ligand; BMM, bone marrow-derived macrophage-like cell; ChIP, chromatin immunoprecipitation; HDAC, histone deacetylase; Luc, luciferase; Mitf, microphthalmia transcription factor; MNC, multinuclear osteoclast; OSCAR, osteoclast-associated receptor; PIAS, protein inhibitor of activated STAT; SUMO, small ubiquitin-like modifier; siRNA, small interference RNA; TRAP, tartrate-resistant acid phosphatase; HA, hemagglutinin.
This article has been cited by other articles:
|
|
 |
|
  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]
|
|
|
|
 |
|
 T. Hikata, H. Takaishi, J. Takito, A. Hakozaki, M. Furukawa, S. Uchikawa, T. Kimura, Y. Okada, M. Matsumoto, A. Yoshimura, et al. PIAS3 negatively regulates RANKL-mediated osteoclastogenesis directly in osteoclast precursors and indirectly via osteoblasts Blood, March 5, 2009; 113(10): 2202 - 2212. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Duplomb, M. Baud'huin, C. Charrier, M. Berreur, V. Trichet, F. Blanchard, and D. Heymann Interleukin-6 Inhibits Receptor Activator of Nuclear Factor {kappa}B Ligand-Induced Osteoclastogenesis by Diverting Cells into the Macrophage Lineage: Key Role of Serine727 Phosphorylation of Signal Transducer and Activator of Transcription 3 Endocrinology, July 1, 2008; 149(7): 3688 - 3697. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
