Evidence map›Paper›PMID 25108526›Full record

ArticleNature medicine2014

Wnt4 signaling prevents skeletal aging and inflammation by inhibiting nuclear factor-κB.

Bo Yu, Jia Chang, Yunsong Liu, Jiong Li, Kareena Kevork, Khalid Al-Hezaimi, Dana T Graves, No-Hee Park, Cun-Yu Wang

Erratum issuedOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 126 papers.

0numbers the graph read from it
0cells of the map it votes in
126citing papers in PubMed
8.3field-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

126 citing papers in PubMed, 249 citations in OpenAlex.

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  12. Osteocytes Produces RANKL Via Wnt-TGFβ Signaling Axis for Osteoclastogenesis.International journal of biological sciences · 2025
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66 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 2 countries.

Bo Yu1] Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, School of Dentistry, University of California Los Angeles (UCLA), Los Angeles, California, USA. [2].
Jia Chang1] Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, School of Dentistry, University of California Los Angeles (UCLA), Los Angeles, California, USA. [2].
Yunsong LiuDepartment of Prosthodontics, School and Hospital of Stomatology, Peking University, Beijing, China.
Jiong LiLaboratory of Molecular Signaling, Division of Oral Biology and Medicine, School of Dentistry, University of California Los Angeles (UCLA), Los Angeles, California, USA.
Kareena KevorkLaboratory of Molecular Signaling, Division of Oral Biology and Medicine, School of Dentistry, University of California Los Angeles (UCLA), Los Angeles, California, USA.
Khalid Al-HezaimiEng. A.B. Research Center for Growth Factors and Bone Regeneration, Division of Periodontology, College of Dentistry, King Saud University, Riyadh, Saudi Arabia.
Dana T GravesDepartment of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
No-Hee Park1] Division of Diagnostic and Surgical Sciences, School of Dentistry, UCLA, Los Angeles, California, USA. [2] Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.
Cun-Yu Wang1] Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, School of Dentistry, University of California Los Angeles (UCLA), Los Angeles, California, USA. [2] Broad Stem Cell Research Center, UCLA, Los Angeles, California, USA. [3] Department of Bioengineering, Henry Samueli School of Engineering and Applied Science, UCLA, Los Angeles, California, USA.
Peking University · CNUniversity of California, Los Angeles · USUniversity of Pennsylvania · US

Funding

Molecular Regulation of Human Dental Stem Cell PropertyR01DE016513 · NIDCR · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WANG, CUN-YU · 2005 to 2019
$6.0M
Wnt-4 inhibits peridontitis by attenuating NF-kBR01DE019412 · NIDCR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WANG, CUN-YU · 2008 to 2021
$5.7M
Molecular Control of MSC differentiation and Bone Formation by KDM4BR01AR063089 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WANG, CUN-YU · 2013 to 2017
$1.6M
UCLA Dentist-Scientist and Oral Health-Researcher Training ProgramR90DE023057 · NIDCR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WONG, DAVID T · 2012 to 2016
$416k
NIAMS NIH HHS AR63089NIAMS NIH HHS R01 AR063089NIDCR NIH HHS DE16513NIDCR NIH HHS DE19412NIDCR NIH HHS R01 DE016513NIDCR NIH HHS R01 DE019412NIDCR NIH HHS R90 DE023057
6 · The paper itself

Abstract

Aging-related bone loss and osteoporosis affect millions of people worldwide. Chronic inflammation associated with aging promotes bone resorption and impairs bone formation. Here we show that Wnt4 attenuates bone loss in osteoporosis and skeletal aging mouse models by inhibiting nuclear factor-κB (NF-κB) via noncanonical Wnt signaling. Transgenic mice expressing Wnt4 from osteoblasts were significantly protected from bone loss and chronic inflammation induced by ovariectomy, tumor necrosis factor or natural aging. In addition to promoting bone formation, Wnt4 inhibited osteoclast formation and bone resorption. Mechanistically, Wnt4 inhibited NF-κB activation mediated by transforming growth factor-β-activated kinase-1 (Tak1) in macrophages and osteoclast precursors independently of β-catenin. Moreover, recombinant Wnt4 alleviated bone loss and inflammation by inhibiting NF-κB in vivo in mouse models of bone disease. Given its dual role in promoting bone formation and inhibiting bone resorption, our results suggest that Wnt4 signaling could be an attractive therapeutic target for treating osteoporosis and preventing skeletal aging.

Indexed as

Signal TransductionAnimalsBone and BonesEstrogensInflammationMiceMice, Inbred C57BLNF-kappa BOsteoporosisOvariectomyTumor Necrosis Factor-alphaWnt4 ProteinEstrogensNF-kappa BTumor Necrosis Factor-alphaWnt4 ProteinWnt4 protein, mouse

Identifiers

PMID25108526
PMCPMC4159424
OpenAlexW2023016113

What OpenQuestion holds

Textmetadata
LicenceTDM
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.