Evidence map›Paper›PMID 27064822›Full record

ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2016

The Actin-Binding Protein Cofilin and Its Interaction With Cortactin Are Required for Podosome Patterning in Osteoclasts and Bone Resorption In Vivo and In Vitro.

Detina Zalli, Lynn Neff, Kenichi Nagano, Nah Young Shin, Walter Witke, Francesca Gori, Roland Baron

Open access · greenAbstract read
In one paragraph

Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.8field-weighted citation impact, top 10% 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

24 citing papers in PubMed, 45 citations in OpenAlex.

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  16. Role of Cofilin in Alzheimer's Disease.Frontiers in cell and developmental biology · 2020
    Review
  17. Review
  18. Forces and constraints controlling podosome assembly and disassembly.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2019
    Article
  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

7 authors at 3 institutions in 3 countries.

Detina ZalliDepartment of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA, USA.
Lynn NeffDepartment of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA, USA.
Kenichi NaganoDepartment of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA, USA.
Nah Young ShinDepartment of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA, USA.
Walter WitkeInstitut für Genetik, Universität Bonn, Bonn, Germany.
Francesca GoriDepartment of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA, USA.
Roland BaronDepartment of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA, USA.
Institute of Infection and Immunity · CAHarvard University · USUniversity of Bonn · DE

Funding

Mechanisms and function of the microtubule podosome connection in osteoclastsR01AR062054 · NIAMS · HARVARD MEDICAL SCHOOL · PI BARON, ROLAND E · 2012 to 2016
$2.8M
NIAMS NIH HHS R01 AR062054
6 · The paper itself

Abstract

The adhesion of osteoclasts (OCs) to bone and bone resorption require the assembly of specific F-actin adhesion structures, the podosomes, and their dense packing into a sealing zone. The OC-specific formation of the sealing zone requires the interaction of microtubule (MT) + ends with podosomes. Here, we deleted cofilin, a cortactin (CTTN)- and actin-binding protein highly expressed in OCs, to determine if it acts downstream of the MT-CTTN axis to regulate actin polymerization in podosomes. Conditional deletion of cofilin in OCs in mice, driven by the cathepsin K promoter (Ctsk-Cre), impaired bone resorption in vivo, increasing bone density. In vitro, OCs were not able to organize podosomes into peripheral belts. The MT network was disorganized, MT stability was decreased, and cell migration impaired. Active cofilin stabilizes MTs and allows podosome belt formation, whereas MT disruption deactivates cofilin via phosphorylation. Cofilin interacts with CTTN in podosomes and phosphorylation of either protein disrupts this interaction, which is critical for belt stabilization and for the maintenance of MT dynamic instability. Accordingly, active cofilin was required to rescue the OC cytoskeletal phenotype in vitro. These findings suggest that the patterning of podosomes into a sealing zone involves the dynamic interaction between cofilin, CTTN, and the MTs + ends. This interaction is critical for the functional organization of OCs and for bone resorption. © 2016 American Society for Bone and Mineral Research.

Indexed as

AcetylationActin Depolymerizing FactorsAnimalsBone ResorptionCortactinGene DeletionGene TargetingHistone Deacetylase 6HumansMaleMiceMicrotubulesOsteoclastsPhenotypePhosphorylationPodosomesActin Depolymerizing FactorsCortactinHdac6 protein, mouseHistone Deacetylase 6ACTINBONECOFILINOSTEOCLASTPODOSOME

Identifiers

PMID27064822
PMCPMC5070801
OpenAlexW2314794990

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.