Evidence map›Paper›PMID 34530313›Full record

ArticleCell calcium2021

Insulin-like growth factor-1 regulates the mechanosensitivity of chondrocytes by modulating TRPV4.

Nicholas Trompeter, Joseph D Gardinier, Victor DeBarros, Mary Boggs, Vimal Gangadharan, William J Cain, Lauren Hurd, Randall L Duncan

Open access · greenAbstract read
In one paragraph

Article in Cell calcium, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.7field-weighted citation impact, top 14% 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

12 citing papers in PubMed, 24 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. [Research progress of chondrocyte mechanotransduction mediated by TRPV4 and PIEZOs].Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi · 2023
    Review
  8. Article
  9. Harnessing Growth Factor Interactions to Optimize Articular Cartilage Repair.Advances in experimental medicine and biology · 2023
    Review
  10. Article
  11. Review
  12. Review
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

8 authors at 2 institutions in 1 country.

Nicholas TrompeterBiomedical Engineering, University of Delaware, Newark, DE, United States.
Joseph D GardinierBiomechanics and Movement Science Program, University of Delaware, Newark, DE, United States; Bone and Joint Center, Henry Ford Hospital, Detroit, MI, United States.
Victor DeBarrosDepartment of Biological Sciences, University of Delaware, Newark, DE, United States.
Mary BoggsDepartment of Biological Sciences, University of Delaware, Newark, DE, United States.
Vimal GangadharanDepartment of Biological Sciences, University of Delaware, Newark, DE, United States.
William J CainDepartment of Biological Sciences, University of Delaware, Newark, DE, United States.
Lauren HurdDepartment of Biological Sciences, University of Delaware, Newark, DE, United States.
Randall L DuncanBiomedical Engineering, University of Delaware, Newark, DE, United States; Biomechanics and Movement Science Program, University of Delaware, Newark, DE, United States; Department of Biological Sciences, University of Delaware, Newark, DE, United States; Department of Biology, University of Michigan-Flint, Flint, MI, United States. Electronic address: duncanra@umich.edu.
University of Delaware · USHenry Ford Hospital · US

Funding

Predictive Modeling & Optimal Control Framework for Model-Based Epidemic Response in DelawareP20GM103446 · NIGMS · UNIVERSITY OF DELAWARE · PI Anjana Narayan Bhat · 2012 to 2026
$67.2M
Subproject Title: Clinical Research Education, Mentoring and Career Development CoreU54GM104941 · NIGMS · UNIVERSITY OF DELAWARE · PI Gregory E Hicks · 2013 to 2026
$60.5M
NIGMS NIH HHS P20 GM103446NIGMS NIH HHS U54 GM104941
6 · The paper itself

Abstract

Both mechanical and biochemical stimulation are required for maintaining the integrity of articular cartilage. However, chondrocytes respond differently to mechanical stimuli in osteoarthritic cartilage when biochemical signaling pathways, such as Insulin-like Growth Factor-1 (IGF-1), are altered. The Transient Receptor Potential Vanilloid 4 (TRPV4) channel is central to chondrocyte mechanotransduction and regulation of cartilage homeostasis. Here, we propose that changes in IGF-1 can modulate TRPV4 channel activity. We demonstrate that physiologic levels of IGF-1 suppress hypotonic-induced TRPV4 currents and intracellular calcium flux by increasing apparent cell stiffness that correlates with actin stress fiber formation. Disruption of F-actin following IGF-1 treatment results in the return of the intracellular calcium response to hypotonic swelling. Using point mutations of the TRPV4 channel at the microtubule-associated protein 7 (MAP-7) site shows that regulation of TRPV4 by actin is mediated via the interaction of actin with the MAP-7 domain of TRPV4. We further highlight that ATP release, a down-stream response to mechanical stimulation in chondrocytes, is mediated by TRPV4 during hypotonic challenge. This response is significantly abrogated with IGF-1 treatment. As chondrocyte mechanosensitivity is greatly altered during osteoarthritis progression, IGF-1 presents as a promising candidate for prevention and treatment of articular cartilage damage.

Indexed as

Cartilage, ArticularChondrocytesCells, CulturedInsulin-Like Growth Factor IMechanotransduction, CellularTRPV Cation ChannelsInsulin-Like Growth Factor ITRPV Cation ChannelsActinChondrocytesHypotonic swellingIGF-1MechanosensitivityTRPV4

Identifiers

PMID34530313
PMCPMC8541913
OpenAlexW3198385866

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.