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ID 119230
タイトル別表記
Role of Netrin 1 in Bone Homeostasis
著者
Maruyama, Kenta Osaka University
Kawasaki, Takahiko National Institute of Genetics
Hamaguchi, Masahide Osaka University
Hashimoto, Motomu Kyoto University
Furu, Moritoshi Kyoto University
Ito, Hiromu Kyoto University
Fujii, Takao Kyoto University
Takemura, Naoki The University of Tokyo
Karuppuchamy, Thangaraj Osaka University
Kondo, Takeshi Osaka University
Kawasaki, Takumi Osaka University
Fukasaka, Masahiro Osaka University
Misawa, Takuma Osaka University
齊藤, 達哉 Osaka University|Tokushima University KAKEN研究者をさがす
Suzuki, Yutaka The University of Tokyo
Martino, Mikaël M. Osaka University|Monash University
Kumagai, Yutaro Osaka University
Akira, Shizuo Osaka University
資料タイプ
学術雑誌論文
抄録
Netrin 1 was initially identified as an axon guidance factor, and recent studies indicate that it inhibits chemokine-directed monocyte migration. Despite its importance as a neuroimmune guidance cue, the role of netrin 1 in osteoclasts is largely unknown. Here we detected high netrin 1 levels in the synovial fluid of rheumatoid arthritis patients. Netrin 1 is potently expressed in osteoblasts and synovial fibroblasts, and IL-17 robustly enhances netrin 1 expression in these cells. The binding of netrin 1 to its receptor UNC5b on osteoclasts resulted in activation of SHP1, which inhibited VAV3 phosphorylation and RAC1 activation. This significantly impaired the actin polymerization and fusion, but not the differentiation of osteoclast. Strikingly, netrin 1 treatment prevented bone erosion in an autoimmune arthritis model and age related bone destruction. Therefore, the netrin 1-UNC5b axis is a novel therapeutic target for bone-destructive diseases.
掲載誌名
Journal of Biological Chemistry
ISSN
00219258
1083351X
cat書誌ID
AA1202441X
出版者
American Society for Biochemistry and Molecular Biology|Elsevier
291
46
開始ページ
23854
終了ページ
23868
発行日
2016-09-28
権利情報
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
先端酵素学研究所