Evidence map›Paper›PMID 37043309›Full record

ArticleMolecular biology of the cell2023

Microenvironmental mechanoactivation through Yap/Taz suppresses chondrogenic gene expression.

Grey F Hallström, Dakota L Jones, Ryan C Locke, Edward D Bonnevie, Sung Yeon Kim, Lorielle Laforest, Diana Cruz Garcia, Robert L Mauck

Open access · greenAbstract read
In one paragraph

Article in Molecular biology of the cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
3.8field-weighted citation impact, top 7% 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

15 citing papers in PubMed, 18 citations in OpenAlex.

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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 2 countries.

Grey F HallströmMcKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine.ORCID 0000-0003-0040-4032
Dakota L JonesMcKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine.
Ryan C LockeMcKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine.
Edward D BonnevieMcKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine.
Sung Yeon KimMcKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine.
Lorielle LaforestMcKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine.
Diana Cruz GarciaMcKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine.
Robert L MauckMcKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine.ORCID 0000-0002-9537-603X
Philadelphia VA Medical Center · USOrthopaedic Research · GB

Funding

Training in Muscle Biology and Muscle DiseaseT32AR053461 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI OSTAP, E. MICHAEL · 2006 to 2025
$4.9M
Engineered Developmental Microenvironments: Cartilage Formation and MaturationR01AR077362 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI BURDICK, JASON A, MAUCK, ROBERT L · 2020 to 2024
$2.5M
Preserving chromatin nano-structure to enhance chondrocyte therapeutic potential for cartilage repairR01AR079224 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI Su Chin Heo, Melike Lakadamyali · 2022 to 2026
$2.0M
Mechanobiology of Progenitor Cells in Heterotopic OssificationR01AR071399 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI MAUCK, ROBERT L, SHORE, EILEEN M · 2018 to 2022
$1.6M
Mechano-Instructive Material Inclusions to Direct Meniscus RepairIK1RX003932 · VA · PHILADELPHIA VA MEDICAL CENTER · PI LOCKE, RYAN C · 2023 to 2023
–
Howard Hughes Medical InstituteNIAMS NIH HHS R01 AR071399NIAMS NIH HHS R01 AR077362NIAMS NIH HHS R01 AR079224NIAMS NIH HHS T32 AR053461RRD VA IK1 RX003932
6 · The paper itself

Abstract

Chondrocyte phenotype is preserved when cells are round and the actin cytoskeleton is cortical. Conversely, these cells rapidly dedifferentiate in vitro with increased mechanoactive Rho signaling, which increases cell size and causes large actin stress fiber to form. While the effects of Rho on chondrocyte phenotype are well established, the molecular mechanism is not yet fully elucidated. Yap, a transcriptional coregulator, is regulated by Rho in a mechanotransductive manner and can suppress chondrogenesis in vivo. Here, we sought to elucidate the relationship between mechanoactive Rho and Yap on chondrogenic gene expression. We first show that decreasing mechanoactive state through Rho inhibition results in a broad increase in chondrogenic gene expression. Next, we show that Yap and its coregulator Taz are negative regulators of chondrogenic gene expression, and removal of these factors promotes chondrogenesis even in environments that promote cell spreading. Finally, we establish that Yap/Taz is essential for translating Rho-mediated signals to negatively regulate chondrogenic gene expression, and that its removal negates the effects of increased Rho signaling. Together, these data indicate that Rho is a mechanoregulator of chondrogenic differentiation, and that its impact on chondrogenic expression is exerted principally through mechanically induced translocation and activity of Yap and Taz.

Indexed as

Adaptor Proteins, Signal TransducingTranscription FactorsChondrogenesisGene ExpressionYAP-Signaling ProteinsAdaptor Proteins, Signal TransducingTranscription FactorsYAP-Signaling Proteins

Identifiers

PMID37043309
PMCPMC10295477
OpenAlexW4365135307

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.