Evidence map›Paper›PMID 41183210›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2025

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

Takeshi Kaneko, Shinya Yari, Junichi Kikuta, Yoshiki Omatsu, Shigeto Seno, Sumire Kikuchi, Kazuma Sato, Kentaro Fujii, Takao Sudo, Tetsuo Hasegawa and 13 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Bone matrix proteins: regulators of skeletal remodeling and repair.Journal of bone and mineral metabolism · 2026
    Review
  5. The RANK/RANKL axis controls vascular dynamics in the bone marrow.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors.

Takeshi Kaneko *Department of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, The University of Osaka, Osaka 565-0871, Japan.ORCID 0009-0005-3576-7679
Shinya Yari *Department of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, The University of Osaka, Osaka 565-0871, Japan.ORCID 0000-0001-7915-5926
Junichi KikutaDepartment of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, The University of Osaka, Osaka 565-0871, Japan.
Yoshiki OmatsuWorld Premier International Research Center Initiative Immunology Frontier Research Center, The University of Osaka, Osaka 565-0871, Japan.ORCID 0000-0002-6212-0441
Shigeto SenoDepartment of Bioinformatic Engineering, Graduate School of Information Science and Technology, The University of Osaka, Osaka 565-0871, Japan.
Sumire KikuchiDepartment of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, The University of Osaka, Osaka 565-0871, Japan.
Kazuma SatoDepartment of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, The University of Osaka, Osaka 565-0871, Japan.
Kentaro FujiiDepartment of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, The University of Osaka, Osaka 565-0871, Japan.ORCID 0000-0002-3692-493X
Takao SudoDepartment of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, The University of Osaka, Osaka 565-0871, Japan.
Tetsuo HasegawaDepartment of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, The University of Osaka, Osaka 565-0871, Japan.
Kunimaro FurutaDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905.
Qianqian GuoDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905.
Samar H IbrahimDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905.ORCID 0000-0001-8470-8337
Kosuke MuraokaGraduate School of Pharmaceutical Sciences, The University of Osaka, Osaka 565-0871, Japan.
Yoshiaki OkadaGraduate School of Pharmaceutical Sciences, The University of Osaka, Osaka 565-0871, Japan.ORCID 0000-0002-2962-244X
Yoshiaki KubotaDepartment of Anatomy, Keio University School of Medicine, Tokyo 160-8582, Japan.ORCID 0000-0001-6672-4122
Daisuke OkuzakiWorld Premier International Research Center Initiative Immunology Frontier Research Center, The University of Osaka, Osaka 565-0871, Japan.ORCID 0000-0002-4552-783X
Yasuhiro KobayashiDepartment of Biochemistry, Matsumoto Dental University, Nagano 399-0704, Japan.ORCID 0000-0002-0903-3226
Atsushi KumanogohDepartment of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, The University of Osaka, Osaka 565-0871, Japan.ORCID 0000-0003-4749-7117
Nobuyuki UdagawaDepartment of Biochemistry, Matsumoto Dental University, Nagano 399-0704, Japan.
Takashi NagasawaWorld Premier International Research Center Initiative Immunology Frontier Research Center, The University of Osaka, Osaka 565-0871, Japan.
Josef M PenningerHelmholtz Centre for Infection Research, Braunschweig, Lower Saxony 38124, Germany.
Masaru IshiiDepartment of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, The University of Osaka, Osaka 565-0871, Japan.ORCID 0000-0002-4215-007X

Funding

Japan Agency for Medical Research and Development (AMED) JP21am0401009Japan Agency for Medical Research and Development (AMED) JP21gm6210005MEXT | Japan Science and Technology Agency (JST) JPMJFR220NMEXT | Japan Society for the Promotion of Science (JSPS) 19H05657MEXT | Japan Society for the Promotion of Science (JSPS) 20H05901MEXT | Japan Society for the Promotion of Science (JSPS) 21H02716MEXT | Japan Society for the Promotion of Science (JSPS) 22H05084MEXT | Japan Society for the Promotion of Science (JSPS) 22H05085MEXT | Japan Society for the Promotion of Science (JSPS) 22K21354
6 · The paper itself

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.

Indexed as

Bone MarrowCapillary PermeabilityRANK LigandReceptor Activator of Nuclear Factor-kappa BAnimalsCapillariesCell DifferentiationDisease Models, AnimalEndothelial CellsFemaleGene Expression RegulationIntercellular Adhesion Molecule-1MiceMice, Inbred C57BLMice, TransgenicOsteoclastsIntercellular Adhesion Molecule-1RANK LigandReceptor Activator of Nuclear Factor-kappa BTnfrsf11a protein, mouseTnfsf11 protein, mouseVascular Cell Adhesion Molecule-1bone marrowbone metabolismintravital imagingRANK/RANKL axisvascular permeability

Identifiers

PMID41183210
PMCPMC12625855

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.