Evidence map›Paper›PMID 37936884›Full record

ArticleExtracellular vesicles and circulating nucleic acids2023

Receptor activator of nuclear factor-kappa B is enriched in CD9-positive extracellular vesicles released by osteoclasts.

Shaobo Ruan, Wellington J Rody, Shivani S Patel, Lina I Hammadi, Macey L Martin, Lorraine P de Faria, George Daaboul, Leif S Anderson, Mei He, L Shannon Holliday

Open access · hybridAbstract read
In one paragraph

Article in Extracellular vesicles and circulating nucleic acids, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.5field-weighted citation impact, top 17% of its field
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

4 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
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

10 authors at 5 institutions in 2 countries.

Shaobo RuanDepartment of Pharmaceutics, College of Pharmacy, Gainesville, FL 32610, USA.
Wellington J RodyDepartment of Orthodontics and Dentofacial Orthopedics, University of Pittsburgh, School of Dental Medicine, Pittsburgh, PA 15261, USA.
Shivani S PatelDepartment of Orthodontics, University of Florida College of Dentistry, Gainesville, FL 32610, USA.
Lina I HammadiDepartment of Orthodontics, University of Florida College of Dentistry, Gainesville, FL 32610, USA.
Macey L MartinDepartment of Orthodontics, University of Florida College of Dentistry, Gainesville, FL 32610, USA.
Lorraine P de FariaDepartment of Biomaterials and Oral Biology, School of Dentistry, University of Säo Paulo, Säo Paulo - SP 05508-000, Brazil.
George DaaboulUnchained Labs, Pleasanton, CA 94588, USA.
Leif S AndersonUnchained Labs, Pleasanton, CA 94588, USA.
Mei HeDepartment of Pharmaceutics, College of Pharmacy, Gainesville, FL 32610, USA.
L Shannon HollidayDepartment of Orthodontics, University of Florida College of Dentistry, Gainesville, FL 32610, USA.
Florida College · USAmerican Association of Colleges of Pharmacy · USUnchained Labs (United States) · USUniversity of Florida · USUniversity of Pittsburgh · US

Funding

Dental applications for a novel osteoclast inhibitorR21DE019862 · NIDCR · UNIVERSITY OF FLORIDA · PI HOLLIDAY, LEXIE SHANNON · 2010 to 2011
$401k
Development of an exosome-based diagnostic platform for periodontal disease and root resorptionR03DE027504 · NIDCR · STATE UNIVERSITY NEW YORK STONY BROOK · PI RODY, WELLINGTON J · 2018 to 2019
$319k
NIDCR NIH HHS R03 DE027504NIDCR NIH HHS R21 DE019862
6 · The paper itself

Abstract

Aim: Receptor activator of nuclear factor-kappa B (RANK)-containing extracellular vesicles (EVs) bind RANK-Ligand (RANKL) on osteoblasts, and thereby simultaneously inhibit bone resorption and promote bone formation. Because of this, they are attractive candidates for therapeutic bone anabolic agents. Previously, RANK was detected in 1 in every 36 EVs from osteoclasts by immunogold electron microscopy. Here, we have sought to characterize the subpopulation of EVs from osteoclasts that contains RANK in more detail. Methods: The tetraspanins CD9 and CD81 were localized in osteoclasts by immunofluorescence. EVs were visualized by transmission electron microscopy. A Single Particle Interferometric Reflectance Imaging Sensor (SP-IRIS) and immunoaffinity isolations examined whether RANK is enriched in specific types of EVs. Results: Immunofluorescence showed CD9 was mostly on or near the plasma membrane of osteoclasts. In contrast, CD81 was localized deeper in the osteoclast's cytosolic vesicular network. By interferometry, both CD9 and CD81 positive EVs from osteoclasts were small (56-83 nm in diameter), consistent with electron microscopy. The CD9 and CD81 EV populations were mostly distinct, and only 22% of the EVs contained both markers. RANK was detected by SP-IRIS in 2%-4% of the CD9-containing EVs, but not in CD81-positive EVs, from mature osteoclasts. Immunomagnetic isolation of CD9-containing EVs from conditioned media of osteoclasts removed most of the RANK. A trace amount of RANK was isolated with CD81. Conclusion: RANK was enriched in a subset of the CD9-positive EVs. The current study provides the first report of selective localization of RANK in subsets of EVs.

Indexed as

boneExosomesmicrovesiclesRANKL reverse signalingremodelingSingle Particle Interferometric Reflectance Imaging Sensor

Identifiers

PMID37936884
PMCPMC10629932
OpenAlexW4388112710

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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 OpenQuestion graph.