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ID 119230
Title Alternative
Role of Netrin 1 in Bone Homeostasis
Author
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
Saitoh, Tatsuya Osaka University|Tokushima University KAKEN Search Researchers
Suzuki, Yutaka The University of Tokyo
Martino, Mikaël M. Osaka University|Monash University
Kumagai, Yutaro Osaka University
Akira, Shizuo Osaka University
Content Type
Journal Article
Description
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.
Journal Title
Journal of Biological Chemistry
ISSN
00219258
1083351X
NCID
AA1202441X
Publisher
American Society for Biochemistry and Molecular Biology|Elsevier
Volume
291
Issue
46
Start Page
23854
End Page
23868
Published Date
2016-09-28
Rights
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Institute of Advanced Medical Sciences