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タイトル: Critical roles of c-Jun signaling in regulation of NFAT family and RANKL-requlated osteoclast differentiation
著者: Ikeda, Fumiyo
Nishimura, Riko
Matsubara, Takuma
Tanaka, Sakae
Inoue, Jun-ichiro
Reddy, Sakamuri V.
Hata, Kenji
Yamashita, Kenji
Hiraga, Toru
Watanabe, Toshiyuki
Kukita, Toshio
Yoshioka, Katsuji link image link image
Rao, Anjana
Yoneda, Toshiyuki
善岡, 克次
発行日: 2004年 8月
出版社(者): American Society for Clinical Investigation
雑誌名: Journal of Clinical Investigation
ISSN: 0021-9738
巻: 114
号: 4
開始ページ: 475
終了ページ: 484
抄録: Receptor activator of NF-κB ligand (RANKL) plays an essential role in osteoclast formation and bone resorption. Although genetic and biochemical studies indicate that RANKL regulates osteoclast differentiation by activating receptor activator of NF-κB and associated signaling molecules, the molecular mechanisms of RANKL-regulated osteoclast differentiation have not yet been fully established. We investigated the role of the transcription factor c-Jun, which is activated by RANKL, in osteoclastogenesis using transgenic mice expressing dominant-negative c-Jun specifically in the osteoclast lineage. We found that the transgenic mice manifested severe osteopetrosis due to impaired osteoclastogenesis. Blockade of c-Jun signaling also markedly inhibited soluble RANKL-induced osteoclast differentiation in vitro. Overexpression of nuclear factor of activated T cells 1 (NFAT1) (NFATc2/ NFATp) or NFAT2 (NFATc1/NFATc) promoted differentiation of osteoclast precursor cells into tartrate-resistant acid phosphatase-positive (TRAP-positive) multinucleated osteoclast-like cells even in the absence of RANKL. Overexpression of NFAT1 also markedly transactivated the TRAP gene promoter. These osteoclastogenic activities of NFAT were abrogated by overexpression of dominant-negative c-Jun. Importantly, osteoclast differentiation and induction of NFAT2 expression by NFAT1 overexpression or soluble RANKL treatment were profoundly diminished in spleen cells of the transgenic mice. Collectively, these results indicate that c-Jun signaling in cooperation with NFAT is crucial for RANKL-regulated osteoclast differentiation.
DOI: 10.1172/JCI200419657
URI: http://hdl.handle.net/2297/16791
関連URI: http://dx.doi.org/10.1172/JCI200419657
資料種別: Journal Article
権利関係: Copyright © 2004, The American Society for Clinical Investigation
版表示: publisher
出現コレクション:1. 査読済論文

このアイテムを引用あるいはリンクする場合は次の識別子を使用してください。 http://hdl.handle.net/2297/16791



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