1. Netrin-4 derived from murine vascular endothelial cells inhibits osteoclast differentiation in vitro and prevents bone loss in vivo.
- Author
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Enoki Y, Sato T, Tanaka S, Iwata T, Usui M, Takeda S, Kokabu S, Matsumoto M, Okubo M, Nakashima K, Yamato M, Okano T, Fukuda T, Chida D, Imai Y, Yasuda H, Nishihara T, Akita M, Oda H, Okazaki Y, Suda T, and Yoda T
- Subjects
- Animals, Bone Resorption metabolism, Cells, Cultured, Coculture Techniques, Endothelium, Vascular pathology, Macrophages metabolism, Mice, Mice, Inbred C57BL, Netrins, Osteoporosis chemically induced, RANK Ligand, Cell Differentiation, Endothelial Cells metabolism, Nerve Growth Factors physiology, Osteoclasts physiology, Osteoporosis metabolism
- 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., (Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)
- Published
- 2014
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