Netrin‐4 derived from murine vascular endothelial cells inhibits osteoclast differentiation in vitro and prevents bone loss in vivo. Issue 14 (17th May 2014)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: FEBS letters. Volume 588:Issue 14(2014)
• Page Start: 2262
• Page End: 2269
• Publication Date: 2014-05-17
• Subjects: M-CSF -- macrophage colony-stimulating factor -- RANKL -- receptor activator of nuclear factor-KB ligand -- TRAP -- tartrate-resistant acid phosphatase -- Osteoclast -- Netrin-4 -- Inhibition -- Vascular endothelial cell; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2014.05.009
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : 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. Abstract : Netrin‐4 inhibits osteoclast differentiation. Vascular endothelial cells inhibit osteoclast differentiation via netrin‐4. Netrin‐4 prevents bone loss in a RANKL‐induced osteoporosis mouse model.