Evidence map›Paper›PMID 27330028›Full record

ArticleJournal of autoimmunity2016

Autophagy-linked FYVE containing protein WDFY3 interacts with TRAF6 and modulates RANKL-induced osteoclastogenesis.

Dennis J Wu, Ran Gu, Ritu Sarin, Regina Zavodovskaya, Chia-Pei Chen, Blaine A Christiansen, Konstantinos S Zarbalis, Iannis E Adamopoulos

Erratum issuedAbstract read
In one paragraph

Article in Journal of autoimmunity, 2016. 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 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
1.7field-weighted citation impact, top 15% 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

23 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Comprehensive analysis of myeloid reporter mice.bioRxiv : the preprint server for biology · 2025
    Article
  9. Article
  10. 14-3-3ζ suppresses RANKL signaling by destabilizing TRAF6.The Journal of biological chemistry · 2024
    Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Nano-sized AlCell death & disease · 2018
    Article
  18. Article
  19. Autoimmunity in 2016.Clinical reviews in allergy & immunology · 2017
    Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Dennis J WuGraduate Group in Immunology, University of California at Davis, United States; Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, United States.
Ran GuDivision of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, United States.
Ritu SarinDivision of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, United States.
Regina ZavodovskayaDepartment of Anatomy, Physiology and Cell Biology, University of California at Davis, United States.
Chia-Pei ChenDepartment of Statistics, University of California at Davis, United States.
Blaine A ChristiansenDepartment of Orthopedic Surgery, University of California at Davis, United States.
Konstantinos S Zarbalis
Iannis E AdamopoulosGraduate Group in Immunology, University of California at Davis, United States; Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, United States; Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Northern California, United States. Electronic address: iannis@ucdavis.edu.
University of California, Davis · USShriners Hospitals for Children - Erie · US

Funding

UCD KOMP PROJECT REPOSITORYU42RR024244 · NCRR · UNIVERSITY OF CALIFORNIA AT DAVIS · PI LLOYD, KC KENT · 2007 to 2010
$7.9M
The IL-23/IL-17 Axis in Inflammatory ArthritisR01AR062173 · NIAMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI LEVY, DAN · 2012 to 2025
$4.9M
Craniofacial Defects in the Manta-Ray Line: A Novel Model for RibosomopathiesR01DE022830 · NIDCR · UNIVERSITY OF CALIFORNIA AT DAVIS · PI ZARBALIS, KONSTANTINOS · 2015 to 2018
$1.5M
NCRR NIH HHS U42 RR024244NIAMS NIH HHS R01 AR062173NIDCR NIH HHS R01 DE022830
6 · The paper itself

Abstract

Recently, autophagy-related proteins were shown to regulate osteoclast mediated bone resorption, a critical process in autoimmune diseases such as rheumatoid arthritis. However, the role of autophagy-linked FYVE containing protein, WDFY3, in osteoclast biology remains elusive. WDFY3 is a master regulator in selective autophagy for clearing ubiquitinated protein aggregates and has been linked with rheumatoid arthritis. Herein, we used a series of WDFY3 transgenic mice (Wdfy3(lacZ) and Wdfy3(loxP)) to investigate the function of WDFY3 in osteoclast development and function. Our data demonstrate that WDFY3 is highly expressed at the growth plate of neonatal mice and is expressed in osteoclasts in vitro cultures. Osteoclasts derived from WDFY3 conditional knockout mice (Wdfy3(loxP/loxP)-LysM-Cre(+)) demonstrated increased osteoclast differentiation as evidenced by higher number and enlarged size of TRAP(+) multinucleated cells. Western blot analysis also revealed up-regulation of TRAF6 and an increase in RANKL-induced NF-κB signaling in WDFY3-deficient bone marrow-derived macrophages compared to wild type cultures. Consistent with these observations WDFY3-deficient cells also demonstrated an increase in osteoclast-related genes Ctsk, Acp5, Mmp9 and an increase of dentine resorption in in vitro assays. Importantly, in vivo RANKL gene transfer exacerbated bone loss in WDFY3 conditional knockout mice, as evidenced by elevated serum TRAP, CTX-I and micro-CT analysis of distal femurs compared to wild type littermates. Taken together, our data highlight a novel role for WDFY3 in osteoclast development and function, which can be exploited for the treatment of musculoskeletal diseases.

Indexed as

Adaptor Proteins, Signal TransducingAnimalsAutophagyAutophagy-Related ProteinsBlotting, WesternBone ResorptionCathepsin KCell DifferentiationCells, CulturedFemurGene Transfer TechniquesGiant CellsMacrophagesMatrix Metalloproteinase 9MiceMice, Inbred C57BLAcp5 protein, mouseAdaptor Proteins, Signal TransducingAutophagy-Related ProteinsCathepsin KCtsk protein, mouseMatrix Metalloproteinase 9Mmp9 protein, mouseNF-kappa BRANK LigandTartrate-Resistant Acid PhosphataseTNF Receptor-Associated Factor 6Tnfsf11 protein, mouseVesicular Transport ProteinsWdfy3 protein, mouseAutophagyAutophagy-linked FYVE containing proteinMusculoskeletal diseasesOsteoclastTRAF6WDFY3

Identifiers

PMID27330028
PMCPMC5003737
OpenAlexW2475221095

What OpenQuestion holds

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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.