The RANK/RANKL axis controls vascular dynamics in the bone marrow
Abstract
Receptor activator of nuclear factor kappa B ligand (RANKL) is an essential cytokine that induces osteoclastic differentiation by monocyte-macrophage lineage precursors. Here, we showed that in addition to its conventional action, RANKL controls vascular permeability in the bone marrow, where it facilitates the mobilization of hematopoietic monocytic cells, including osteoclast precursors, and resultantly regulates bone metabolism. RANK, a cognate receptor for RANKL, is abundantly expressed in sinusoidal endothelial cells and controls vascular permeability by regulating the expression patterns of intercellular adhesion molecule 1 and vascular cell adhesion molecule 1. High RANKL expression was detected in perivascular C–X–C motif chemokine ligand 12-abundant reticular (CAR) stromal cells. Specific deletion of RANKL expression in CAR cells abrogated the vascular leakage, suggesting that perivascular RANKL is responsible for controlling permeability. In summary, our study revealed a role for RANK/RANKL signaling as a gatekeeper of bone marrow sinusoids in vivo.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (23)
Takeshi Kaneko
Department of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, The University of Osaka
Shinya Yari
Department of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, The University of Osaka
Junichi Kikuta
Department of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, The University of Osaka
Yoshiki Omatsu
World Premier International Research Center Initiative Immunology Frontier Research Center, The University of Osaka
Shigeto Seno
Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, The University of Osaka
Sumire Kikuchi
Department of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, The University of Osaka
Kazuma Sato
Department of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, The University of Osaka
Kentaro Fujii
Department of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, The University of Osaka
Takao Sudo
Department of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, The University of Osaka
Tetsuo Hasegawa
Department of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, The University of Osaka
Kunimaro Furuta
Division of Gastroenterology and Hepatology, Mayo Clinic
Qianqian Guo
Division of Gastroenterology and Hepatology, Mayo Clinic
Samar H. Ibrahim
Division of Gastroenterology and Hepatology, Mayo Clinic
Kosuke Muraoka
Graduate School of Pharmaceutical Sciences, The University of Osaka
Yoshiaki Okada
Graduate School of Pharmaceutical Sciences, The University of Osaka
Yoshiaki Kubota
Department of Anatomy, Keio University School of Medicine
Daisuke Okuzaki
Yasuhiro Kobayashi
Institute for Integrated Radiation and Nuclear Science, Kyoto University, Kumatori, Osaka 590-0494, Japan
Atsushi Kumanogoh
Nobuyuki Udagawa
Department of Biochemistry, Matsumoto Dental University
Takashi Nagasawa
World Premier International Research Center Initiative Immunology Frontier Research Center, The University of Osaka
Josef M. Penninger
Helmholtz Centre for Infection Research
Masaru Ishii
Department of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, The University of Osaka