Evidence map›Paper›PMID 33758201›Full record

ArticleNature communications2021

Osteoclasts protect bone blood vessels against senescence through the angiogenin/plexin-B2 axis.

Xiaonan Liu, Yu Chai, Guanqiao Liu, Weiping Su, Qiaoyue Guo, Xiao Lv, Peisong Gao, Bin Yu, Gerardo Ferbeyre, Xu Cao and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed, 1 pooled it
7.0field-weighted citation impact, top 2% 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

85 citing papers in PubMed, 1 synthesis or guideline pooled it, 108 citations in OpenAlex.

  1. Pooled it
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  13. [Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026
    Article
  14. [Early effectiveness of total talar replacement with three-dimensional-printed talus prostheses in steroid-induced talar avascular necrosis].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2026
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25 more citing papers are in PubMed but not listed here.

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

11 authors at 3 institutions in 3 countries.

Xiaonan Liu *Department of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0003-3661-7961
Yu Chai *Department of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0003-4042-1814
Guanqiao LiuDepartment of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0003-4119-3796
Weiping SuDepartment of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Qiaoyue GuoDepartment of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Xiao LvDepartment of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-0175-5240
Peisong GaoJohns Hopkins Asthma & Allergy Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-7651-1339
Bin YuDivision of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Gerardo FerbeyreDepartment of Biochemistry and Molecular Medicine, Université de Montréal, Montreal, QC, Canada.ORCID http://orcid.org/0000-0002-2146-618X
Xu CaoDepartment of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0001-8614-6059
Mei WanDepartment of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. mwan4@jhmi.edu.ORCID http://orcid.org/0000-0001-9404-540X
Johns Hopkins University · USNanfang Hospital · CNUniversité de Montréal · CA

Funding

Skeleton and Joint Degeneration with AgingP01AG066603 · NIA · JOHNS HOPKINS UNIVERSITY · PI CAO, XU · 2021 to 2025
$9.2M
Zeiss LSM780 Confocal Microscope for a Core FacilityS10OD016374 · OD · JOHNS HOPKINS UNIVERSITY · PI KUO, SCOT CHARLES · 2013 to 2013
$584k
Pre-osteoclasts in Vascular AgingR56AG059578 · NIA · JOHNS HOPKINS UNIVERSITY · PI WAN, MEI · 2018 to 2018
$409k
NIA NIH HHS P01 AG066603NIA NIH HHS R56 AG059578NIH HHS S10 OD016374
6 · The paper itself

Abstract

Synthetic glucocorticoids (GCs), one of the most effective treatments for chronic inflammatory and autoimmune conditions in children, have adverse effects on the growing skeleton. GCs inhibit angiogenesis in growing bone, but the underlying mechanisms remain unclear. Here, we show that GC treatment in young mice induces vascular endothelial cell senescence in metaphysis of long bone, and that inhibition of endothelial cell senescence improves GC-impaired bone angiogenesis with coupled osteogenesis. We identify angiogenin (ANG), a ribonuclease with pro-angiogenic activity, secreted by osteoclasts as a key factor for protecting the neighboring vascular cells against senescence. ANG maintains the proliferative activity of endothelial cells through plexin-B2 (PLXNB2)-mediated transcription of ribosomal RNA (rRNA). GC treatment inhibits ANG production by suppressing osteoclast formation in metaphysis, resulting in impaired endothelial cell rRNA transcription and subsequent cellular senescence. These findings reveal the role of metaphyseal blood vessel senescence in mediating the action of GCs on growing skeleton and establish the ANG/PLXNB2 axis as a molecular basis for the osteoclast-vascular interplay in skeletal angiogenesis.

Indexed as

AnimalsApoptosisBone DevelopmentCell ProliferationCellular SenescenceEndothelial CellsGlucocorticoidsHumansHuman Umbilical Vein Endothelial CellsImmunohistochemistryIn Situ Hybridization, FluorescenceMethylprednisoloneMiceMice, Inbred BALB CMice, Inbred C57BLNeovascularization, PathologicangiogeninGlucocorticoidsMethylprednisoloneNerve Tissue ProteinsPlxnb2 protein, mouseRecombinant ProteinsRibonuclease, PancreaticRNA, RibosomalRNA, Small Interfering

Identifiers

PMID33758201
PMCPMC7987975
OpenAlexW3138375299

What OpenQuestion holds

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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 OpenQuestion graph.