Evidence map›Paper›PMID 39253450›Full record

ArticlebioRxiv : the preprint server for biology2024

Actin Polymerization Status Regulates Tendon Homeostasis through Myocardin-Related Transcription Factor-A.

Valerie C West, Kaelyn Owen, Kameron L Inguito, Karl Matthew M Ebron, Tori Reiner, Chloe E Mirack, Christian Le, Rita de Cassia Marqueti, Steven Snipes, Rouhollah Mousavizadeh and 2 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Valerie C WestDepartment of Biomedical Engineering, University of Delaware, Newark, DE, USA.
Kaelyn OwenDepartment of Biomedical Engineering, University of Delaware, Newark, DE, USA.
Kameron L InguitoDepartment of Biological Sciences, University of Delaware, Newark, DE, USA.
Karl Matthew M EbronDepartment of Kinesiology and Applied Physiology, University of DE, USA.
Tori ReinerDepartment of Biological Sciences, University of Delaware, Newark, DE, USA.
Chloe E MirackDepartment of Biological Sciences, University of Delaware, Newark, DE, USA.
Christian LeDepartment of Biomedical Engineering, University of Delaware, Newark, DE, USA.
Rita de Cassia MarquetiLaboratory of Molecular Analysis, Graduate Program of Rehabilitation Sciences, University of Brasília, Brasília, Distrito Federal, Brazil.
Steven SnipesDepartment of Biological Sciences, University of Delaware, Newark, DE, USA.
Rouhollah MousavizadehDepartment of Physical Therapy, Faculty of Medicine, The University of British Columbia, Vancouver, Canada.
Dawn M ElliottDepartment of Biomedical Engineering, University of Delaware, Newark, DE, USA.ORCID 0000-0003-4792-1029
Justin ParrenoDepartment of Biomedical Engineering, University of Delaware, Newark, DE, USA.ORCID 0000-0001-5277-6255

Funding

Predictive Modeling & Optimal Control Framework for Model-Based Epidemic Response in DelawareP20GM103446 · NIGMS · UNIVERSITY OF DELAWARE · PI MELINDA K DUNCAN · 2012 to 2026
$67.2M
Understanding synovial macrophage inflamm-aging within osteoarthritisP20GM139760 · NIGMS · UNIVERSITY OF DELAWARE · PI DAWN M ELLIOTT · 2021 to 2026
$19.1M
Multiscale tendon damage and aberrant cellular responses in an in vivo model of tendinosisR01AR080059 · NIAMS · UNIVERSITY OF DELAWARE · PI DAWN M ELLIOTT · 2022 to 2026
$2.3M
NIAMS NIH HHS R01 AR080059NIGMS NIH HHS P20 GM103446NIGMS NIH HHS P20 GM139760
6 · The paper itself

Abstract

The actin cytoskeleton is a potent regulator of tenocyte homeostasis. However, the mechanisms by which actin regulates tendon homeostasis are not entirely known. This study examined the regulation of tenocyte molecule expression by actin polymerization via the globular (G-) actin-binding transcription factor, myocardin-related transcription factor-a (MRTF). We determined that decreasing the proportion of G-actin in tenocytes by treatment with TGFβ1 increases nuclear MRTF. These alterations in actin polymerization and MRTF localization coincided with favorable alterations to tenocyte gene expression. In contrast, latrunculin A increases the proportion of G-actin in tenocytes and reduces nuclear MRTF, causing cells to acquire a tendinosis-like phenotype. To parse out the effects of F-actin depolymerization from regulation by MRTF, we treated tenocytes with cytochalasin D. Similar to latrunculin A treatment, exposure of cells to cytochalasin D increases the proportion of G-actin in tenocytes. However, unlike latrunculin A treatment, cytochalasin D increases nuclear MRTF. Compared to latrunculin A treatment, cytochalasin D led to opposing effects on the expression of a subset of genes. The differential regulation of genes by latrunculin A and cytochalasin D suggests that actin signals through MRTF to regulate a specific subset of genes. By targeting the deactivation of MRTF through the inhibitor CCG1423, we verify that MRTF regulates Type I Collagen, Tenascin C, Scleraxis, and α-smooth muscle actin in tenocytes. Actin polymerization status is a potent regulator of tenocyte homeostasis through the modulation of several downstream pathways, including MRTF. Understanding the regulation of tenocyte homeostasis by actin may lead to new therapeutic interventions against tendinopathies, such as tendinosis.

Identifiers

PMID39253450
PMCPMC11383320

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.