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. © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Enoki, Y., Sato, T., Tanaka, S., Iwata, T., Usui, M., Takeda, S., … Yoda, T. (2014). Netrin-4 derived from murine vascular endothelial cells inhibits osteoclast differentiation in vitro and prevents bone loss in vivo. FEBS Letters, 588(14), 2262–2269. https://doi.org/10.1016/j.febslet.2014.05.009