The RANK/RANKL axis controls vascular dynamics in the bone marrow

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.

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Publication Details

Journal
Proceedings of the National Academy of Sciences
Published
2025-11-03
DOI
https://doi.org/10.1073/pnas.2425366122
Citations
2
Primary Topic
Bone Metabolism and Diseases
Type
article
Field-Weighted Citation Impact
1.61
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article

The RANK/RANKL axis controls vascular dynamics in the bone marrow

Daisuke Okuzaki, Junichi Kikuta, Yoshiki Omatsu, Takao Sudo et al.
2 citations
Proceedings of the National Academy of Sciences
Bone Metabolism and Diseases
1.61
article

The RANK/RANKL axis controls vascular dynamics in the bone marrow

Daisuke Okuzaki, Junichi Kikuta, Yoshiki Omatsu, Takao Sudo, Shinya Yari, Kunimaro Furuta, Atsushi Kumanogoh, Kentaro Fujii, Nobuyuki Udagawa, Yoshiaki Kubota, Shigeru Kikuchi, Shigeto Seno, Kazuma Sato, Kosuke Muraoka, Yoshiaki Okada, Yasuhiro Kobayashi, Masaru Ishii, Josef Penninger, Qianqian Guo, Samar H. Ibrahim, Takashi Nagasawa, Tetsuo Hasegawa, Takeshi Kaneko
article en
2 citations

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.

Proceedings of the National Academy of SciencesVol. 122(45)
University of British Columbia (CA), Keio University (JP), Ube Frontier University (JP), Osaka City University (JP), National Institute of Biomedical Innovation, Health and Nutrition (JP), Helmholtz Centre for Infection Research (DE), Mayo Clinic in Arizona (US), Open Medicine Institute (US), Osaka International University (JP), Medical University of Vienna (AT), Osaka University of Pharmaceutical Sciences (JP), Matsumoto Dental University (JP), The University of Osaka (JP)
Openalex Percentile: Top 14%
Bone Metabolism and Diseases
1.61
DOIOpen Access PDFOpenAlex
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