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Netrin‐4 derived from murine vascular endothelial cells inhibits osteoclast differentiation in vitro and prevents bone loss in vivo
Author(s) -
Enoki Yuichiro,
Sato Tsuyoshi,
Tanaka Shinya,
Iwata Takanori,
Usui Michihiko,
Takeda Shu,
Kokabu Shoichiro,
Matsumoto Masahito,
Okubo Masahiko,
Nakashima Keisuke,
Yamato Masayuki,
Okano Teruo,
Fukuda Toru,
Chida Dai,
Imai Yuuki,
Yasuda Hisataka,
Nishihara Tatsuji,
Akita Masumi,
Oda Hiromi,
Okazaki Yasushi,
Suda Tatsuo,
Yoda Tetsuya
Publication year - 2014
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2014.05.009
Subject(s) - in vivo , osteoclast , in vitro , microbiology and biotechnology , chemistry , netrin , biology , immunology , biochemistry , genetics , axon guidance , axon
Bone is a highly vascularized organ, thus angiogenesis is a vital process during bone remodeling. However, the role of vascular systems in bone remodeling is not well recognized. Here we show that netrin‐4 inhibits osteoclast differentiation in vitro and in vivo. Co‐cultures of bone marrow macrophages with vascular endothelial cells markedly inhibited osteoclast differentiation. Adding a neutralizing antibody, or RNA interference against netrin‐4, restored in vitro osteoclast differentiation. Administration of netrin‐4 prevented bone loss in an osteoporosis mouse model by decreasing the osteoclast number. We propose that vascular endothelial cells interact with bone in suppressing bone through netrin‐4.