@article{oai:kanazawa-u.repo.nii.ac.jp:00027547,
 author = {善岡, 克次 and Ikeda, Fumiyo and Nishimura, Riko and Matsubara, Takuma and Tanaka, Sakae and Inoue, Jun-ichiro and Reddy, Sakamuri V. and Hata, Kenji and Yamashita, Kenji and Hiraga, Toru and Watanabe, Toshiyuki and Kukita, Toshio and Yoshioka, Katsuji and Rao, Anjana and Yoneda, Toshiyuki},
 issue = {4},
 journal = {Journal of Clinical Investigation},
 month = {Aug},
 note = {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., 金沢大学がん研究所がん分子細胞制御},
 pages = {475--484},
 title = {Critical roles of c-Jun signaling in regulation of NFAT family and RANKL-requlated osteoclast differentiation},
 volume = {114},
 year = {2004}
}