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学科主题: 临床医学
题名:
AG490 inhibits NFATc1 expression and STAT3 activation during RANKL induced osteoclastogenesis
作者: Li, Chang-hong; Zhao, Jin-xia; Sun, Lin; Yao, Zhong-qiang; Deng, Xiao-li; Liu, Rui; Liu, Xiang-yuan
关键词: Osteoclastogenesis ; AG490 ; RANKL ; NFATc1 ; JAK2/STAT3
刊名: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
发表日期: 2013-06-14
DOI: 10.1016/j.bbrc.2013.04.084
卷: 435, 期:4, 页:533-539
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Biophysics
研究领域[WOS]: Biochemistry & Molecular Biology ; Biophysics
关键词[WOS]: OSTEOPROTEGERIN LIGAND ; RHEUMATOID-ARTHRITIS ; SIGNALING PATHWAYS ; NUCLEAR-FACTOR ; JAK INHIBITOR ; C-FOS ; DIFFERENTIATION ; CELLS ; IMMUNE ; OSTEOIMMUNOLOGY
英文摘要:

Commonly, JAK/STAT relays cytokine signals for cell activation and proliferation, and recent studies have shown that the elevated expression of JAK/STAT is associated with the immune rejection of allografts and the inflammatory processes of autoimmune disease. However, the role which JAK2/STAT3 signaling plays in the receptor activator of nuclear factor-kappa B ligand (RANKL)-mediated osteoclastogenesis is unknown. In this study, we investigated the effects of AG490, specific JAK2 inhibitor, on osteoclast differentiation in vitro. AG490 significantly inhibited osteoclastogenesis in murine osteoclast precursor cell line RAW264.7 induced by RANKL. AG490 suppressed cell proliferation and delayed the G1 to S cell cycle transition. Furthermore, AG490 also suppressed the expression of nuclear factor of activated T cells (NFAT) c1 but not c-Fos in RAW264.7. Subsequently, we investigated various intracellular signaling components associated with osteoclastogenesis. AG490 had no effects on RANKL-induced activation of Akt, ERK1/2. Interestingly, AG490 partly inhibited RANKL-induced phosphorylation of Ser(727) in STAT3. Additionally, down-regulation of STAT3 using siRNA resulted in suppression of TRAP, RANK and NFATc1 expression. In conclusion, we demonstrated that AG490 inhibited RANKL-induced osteoclastogenesis by suppressing NFATc1 production and cell proliferation via the STAT3 pathway. These results suggest that inhibition of JAK2 may be useful for the treatment of bone diseases characterized by excessive osteoclastogenesis. (c) 2013 Elsevier Inc. All rights reserved.

语种: 英语
所属项目编号: 81072474 ; 81102255 ; 7112143
项目资助者: National Natural Science Foundation of China ; National Young Scholars Foundation of China ; Beijing Municipal Natural Science Foundation
WOS记录号: WOS:000321025800005
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/56212
Appears in Collections:北京大学第三临床医学院_期刊论文

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作者单位: Peking Univ, Hosp 3, Dept Rheumatol & Immunol, Beijing 100191, Peoples R China

Recommended Citation:
Li, Chang-hong,Zhao, Jin-xia,Sun, Lin,et al. AG490 inhibits NFATc1 expression and STAT3 activation during RANKL induced osteoclastogenesis[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2013,435(4):533-539.
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