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Blood, 15 August 2005, Vol. 106, No. 4, pp. 1240-1245. Prepublished online as a Blood First Edition Paper on April 28, 2005; DOI 10.1182/blood-2004-12-4975. This Article Full Text (PDF) All Versions of this Article: 2004-12-4975v1 106/4/1240    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 Han, S. Y Articles by Lee, S. Y Search for Related Content PubMed PubMed Citation Articles by Han, S. Y Articles by Lee, S. Y Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 3, 2005 Accepted April 15, 2005 Transcriptional induction of cyclooxygenase-2 in osteoclast precursors is involved in RANKL-induced osteoclastogenesis Song Y Han, Na K Lee, Kyung H Kim, In W Jang, Mijung Yim, Jae H Kim, Won J Lee, and Soo Y Lee* Division of Molecular Life Sciences and Center for Cell Signaling Research, Ewha Womans University, Seoul, Korea, Republic of College of Pharmacy, Sookmyung Women's University, Seoul, Korea, Republic of School of Life Sciences and Biotechnology, Korea University, Seoul, Korea, Republic of * Corresponding author; email: leesy{at}ewha.ac.kr. Regulation of osteoclast differentiation is key to understanding the pathogenesis and to developing treatments for bone diseases such as osteoporosis. To gain insight into the mechanism of the RANKL-specific induction of the osteoclast differentiation program, we took suppression-subtractive hybridization screening approach to identify genes specifically induced via RANKL-Rac1 signaling pathway. Among identified targets, we show that RANKL selectively induces cyclooxygenase (COX)-2 expression via Rac1 that results in turn in PGE2 production in RAW 264.7 cells. By using transient transfection assays, we found that the -233/-206 region of the COX-2 promoter gene was critical for RANKL-induced promoter activity. This RANKL-responsive region contained a NF-B site that, when mutated, completely abolished the induction of NF-B DNA binding activity by RANKL. Blockade of COX-2 by celecoxib inhibits differentiation of bone marrow-derived monocyte/macrophage precursor cells (BMMs) into TRAP-positive osteoclastic cells. This inhibition can be rescued by the addition of exogenous PGE2, suggesting that COX-2-dependent PGE2 induction by RANKL in osteoclast precursors is required for osteoclast differentiation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Cox-2 RANKs high in osteoclastogenesis Elizabeth Olmsted-Davis Blood 2005 106: 1144-1145. [Full Text] [PDF] This article has been cited by other articles: S. D. Yogesha, S. M. Khapli, R. K. Srivastava, L. S. Mangashetti, S. T. Pote, G. C. Mishra, and M. R. Wani IL-3 Inhibits TNF-{alpha}-Induced Bone Resorption and Prevents Inflammatory Arthritis J. Immunol., January 1, 2009; 182(1): 361 - 370. [Abstract] [Full Text] [PDF] B. Hoang, L. Zhu, Y. Shi, P. Frost, H. Yan, S. Sharma, S. Sharma, L. Goodglick, S. Dubinett, and A. Lichtenstein Oncogenic RAS mutations in myeloma cells selectively induce cox-2 expression, which participates in enhanced adhesion to fibronectin and chemoresistance Blood, June 1, 2006; 107(11): 4484 - 4490. [Abstract] [Full Text] [PDF]

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