Evidence map›Paper›PMID 19401766›Full record

ArticlePloS one2009

Non-canonical Wnt signaling and N-cadherin related beta-catenin signaling play a role in mechanically induced osteogenic cell fate.

Emily J Arnsdorf, Padmaja Tummala, Christopher R Jacobs

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed
6.7field-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

86 citing papers in PubMed, 179 citations in OpenAlex.

  1. Review
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  10. Mechanically Robust Hydrogels Facilitating Bone Regeneration through Epigenetic Modulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022
    Article
  11. Review
  12. Article
  13. Regulation of Limbal Epithelial Stem Cells: Importance of the Niche.International journal of molecular sciences · 2021
    Review
  14. Review
  15. Adenylyl cyclase 3 regulates osteocyte mechanotransduction and primary cilium.Biochemical and biophysical research communications · 2021
    Article
  16. Roles of Non-Canonical Wnt Signalling Pathways in Bone Biology.International journal of molecular sciences · 2021
    Review
  17. Article
  18. Article
  19. Review
  20. Article

26 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

3 authors at 2 institutions in 1 country.

Emily J ArnsdorfBone and Joint R&D Center, VA Palo Alto Health Care System, Palo Alto, California, United States of America. emily.arnsdorf@gmail.com
Padmaja Tummala
Christopher R Jacobs
VA Palo Alto Health Care System · USColumbia University · US

Funding

MECHANOTRANSDUCTION IN BONE VIA OSCILLATING FLUID FLOWR01AR045989 · NIAMS · STANFORD UNIVERSITY · PI JACOBS, CHRISTOPHER RAE · 2000 to 2009
$2.4M
NIAMS NIH HHS AR45989NIAMS NIH HHS R01 AR045989
6 · The paper itself

Abstract

backgroundUnderstanding how the mechanical microenvironment influences cell fate, and more importantly, by what molecular mechanisms, will enhance not only the knowledge of mesenchymal stem cell biology but also the field of regenerative medicine. Mechanical stimuli, specifically loading induced oscillatory fluid flow, plays a vital role in promoting healthy bone development, homeostasis and morphology. Recent studies suggest that such loading induced fluid flow has the potential to regulate osteogenic differentiation via the upregulation of multiple osteogenic genes; however, the molecular mechanisms involved in the transduction of a physical signal into altered cell fate have yet to be determined. METHODS AND PRINCIPAL

findingsUsing immuno-staining, western blot analysis and luciferase assays, we demonstrate the oscillatory fluid flow regulates beta-catenin nuclear translocation and gene transcription. Additionally, real time RT-PCR analysis suggests that flow induces Wnt5a and Ror2 upregulation, both of which are essential for activating the small GTPase, RhoA, upon flow exposure. Furthermore, although beta-catenin phosphorylation is not altered by flow, its association with N-cadherin is, indicating that flow-induced beta-catenin signaling is initiated by adherens junction signaling.

conclusionWe propose that the mechanical microenvironment of bone has the potential to regulate osteogenic differentiation by initiating multiple key molecular pathways that are essential for such lineage commitment. Specifically, non-canonical Wnt5a signaling involving Ror2 and RhoA as well as N-cadherin mediated beta-catenin signaling are necessary for mechanically induced osteogenic differentiation.

Indexed as

Adherens JunctionsAnimalsBase Sequencebeta CateninBiomechanical PhenomenaCadherinsCell DifferentiationCell LineMesenchymal Stem CellsMiceModels, BiologicalOsteogenesisReceptor Protein-Tyrosine KinasesReceptor Tyrosine Kinase-like Orphan ReceptorsrhoA GTP-Binding Proteinrho GTP-Binding Proteinsbeta CateninCadherinsCdh2 protein, mouseCTNNB1 protein, mouseReceptor Protein-Tyrosine KinasesReceptor Tyrosine Kinase-like Orphan ReceptorsrhoA GTP-Binding ProteinRhoA protein, mouserho GTP-Binding ProteinsRNA, Small InterferingRor2 protein, mouseWnt-5a ProteinWnt5a protein, mouseWnt Proteins

Identifiers

PMID19401766
PMCPMC2670536
OpenAlexW2168730320

What OpenQuestion holds

Textmetadata
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.