Evidence map›Paper›PMID 25712254›Full record

ArticleCalcified tissue international2015

Ubiquitin E3 Ligase LNX2 is Critical for Osteoclastogenesis In Vitro by Regulating M-CSF/RANKL Signaling and Notch2.

Jian Zhou, Toshifumi Fujiwara, Shiqiao Ye, Xiaolin Li, Haibo Zhao

Open access · greenAbstract read
In one paragraph

Article in Calcified tissue international, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

22 citing papers in PubMed, 33 citations in OpenAlex.

  1. Review
  2. Myeloid-Specific Deletion ofBiomedicines · 2026
    Article
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  5. Review
  6. Impaired Blastocyst Formation inInternational journal of molecular sciences · 2023
    Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Deubiquitinating Enzymes and Bone Remodeling.Stem cells international · 2018
    Review
  16. Article
  17. Article
  18. Notch Signaling and the Skeleton.Endocrine reviews · 2016
    Review
  19. Article
  20. 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

5 authors at 2 institutions in 2 countries.

Jian ZhouDepartment of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Xuhui District, Shanghai, 200233, People's Republic of China.
Toshifumi Fujiwara
Shiqiao Ye
Xiaolin Li
Haibo Zhao
University of Arkansas for Medical Sciences · USShanghai Jiao Tong University · CN

Funding

TRANSGENIC MOUSE COREP01AG013918 · NIA · UNIV OF ARKANSAS FOR MED SCIS · PI O'BRIEN, CHARLES A · 1996 to 2016
$25.7M
Mechanisms of Cytoskeletal and Lysosomal Protein Regulation in OsteoclastsR01AR062012 · NIAMS · UNIV OF ARKANSAS FOR MED SCIS · PI ZHAO, HAIBO · 2011 to 2015
$1.6M
NIAMS NIH HHS AR062012NIAMS NIH HHS R01 AR062012NIA NIH HHS P01 AG013918NIA NIH HHS P01 AG13918
6 · The paper itself

Abstract

The Notch signaling pathway plays a crucial role in skeletal development and homeostasis by regulating the proliferation and differentiation of osteoblasts and osteoclasts. However, the molecular mechanisms modulating the level and activity of Notch receptors in bone cells remain unknown. In this study, we uncovered that LNX2, an E3 ubiquitin ligase and Notch inhibitor Numb binding protein, was up-regulated during osteoclast differentiation. Knocking-down LNX2 expression in bone marrow macrophages by lentivirus-mediated short hairpin RNAs markedly inhibited osteoclast formation. Decreased LNX2 expression attenuated macrophage colony-stimulating factor (M-CSF)-induced ERK and AKT activation and RANKL-stimulated activation of NF-κB and JNK pathways; therefore, accelerated osteoclast apoptosis. Additionally, loss of LNX2 led to an increased accumulation of Numb, which promoted the degradation of Notch and caused a reduction of the expression of the Notch downstream target gene, Hes1. We conclude that LNX2 regulates M-CSF/RANKL and the Notch signaling pathways during osteoclastogenesis.

Indexed as

AnimalsApoptosisCarrier ProteinsCell DifferentiationCell ProliferationFluorescent Antibody TechniqueGene Expression RegulationImmunoblottingIntracellular Signaling Peptides and ProteinsIn Vitro TechniquesMacrophage Colony-Stimulating FactorMiceMice, Inbred C57BLOsteoclastsRANK LigandReal-Time Polymerase Chain ReactionCarrier ProteinsIntracellular Signaling Peptides and ProteinsLnx2 protein, mouseMacrophage Colony-Stimulating FactorNotch2 protein, mouseRANK LigandReceptor, Notch2Tnfsf11 protein, mouse

Identifiers

PMID25712254
PMCPMC4730947
OpenAlexW1965523334

What OpenQuestion holds

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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.