Evidence map›Paper›PMID 25446627›Full record

ArticleStem cells (Dayton, Ohio)2015

TWIST1 silencing enhances in vitro and in vivo osteogenic differentiation of human adipose-derived stem cells by triggering activation of BMP-ERK/FGF signaling and TAZ upregulation.

Natalina Quarto, Kshemendra Senarath-Yapa, Andrea Renda, Michael T Longaker

Open access · bronzeAbstract read
In one paragraph

Article in Stem cells (Dayton, Ohio), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
3.0field-weighted citation impact, top 9% 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

31 citing papers in PubMed, 67 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

4 authors at 2 institutions in 2 countries.

Natalina QuartoHagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Stanford University, School of Medicine, Stanford, California, USA; Dipartimento di Scienze Biomediche Avanzate, Universita' degli Studi di Napoli Federico II, Napoli, Italy.
Kshemendra Senarath-Yapa
Andrea Renda
Michael T Longaker
Stanford University · USUniversity of Naples Federico II · IT

Funding

Induced pluripotent stem cells in the understanding and treatment of heart diseaseU01HL099776 · NHLBI · STANFORD UNIVERSITY · PI LONGAKER, MICHAEL T, WU, JOSEPH C. · 2009 to 2015
$8.2M
Osteogenic Enrichment of Adipose Derived Stromal CellsR01DE021683 · NIDCR · STANFORD UNIVERSITY · PI GURTNER, GEOFFREY C, LONGAKER, MICHAEL T · 2012 to 2016
$2.0M
Regional differences in neural crest and mesodermal derived calvarial bone healinR01DE019434 · NIDCR · STANFORD UNIVERSITY · PI LONGAKER, MICHAEL T · 2010 to 2013
$1.5M
NHLBI NIH HHS U01 HL099776NHLBI NIH HHS U01HL099776NIDCR NIH HHS R01 DE019434NIDCR NIH HHS R01 DE021683NIDCR NIH HHS R01 DE021683-01NIDCR NIH HHS R01 DE19434
6 · The paper itself

Abstract

Mesenchymal stem cells (MSCs) show promise for cellular therapy and regenerative medicine. Human adipose tissue-derived stem cells (hASCs) represent an attractive source of seed cells in bone regeneration. How to effectively improve osteogenic differentiation of hASCs in the bone tissue engineering has become a very important question with profound translational implications. Numerous regulatory pathways dominate osteogenic differentiation of hASCs involving transcriptional factors and signaling molecules. However, how these factors combine with each other to regulate hASCs osteogenic differentiation still remains to be illustrated. The highly conserved developmental proteins TWIST play key roles for transcriptional regulation in mesenchymal cell lineages. This study investigates TWIST1 function in hASCs osteogenesis. Our results show that TWIST1 shRNA silencing increased the osteogenic potential of hASCs in vitro and their skeletal regenerative ability when applied in vivo. We demonstrate that the increased osteogenic capacity observed with TWIST1 knockdown in hASCs is mediated through endogenous activation of BMP and ERK/FGF signaling leading, in turn, to upregulation of TAZ, a transcriptional modulator of MSCs differentiation along the osteoblast lineage. Inhibition either of BMP or ERK/FGF signaling suppressed TAZ upregulation and the enhanced osteogenesis in shTWIST1 hASCs. Cosilencing of both TWIST1 and TAZ abrogated the effect elicited by TWIST1 knockdown thus, identifying TAZ as a downstream mediator through which TWIST1 knockdown enhanced osteogenic differentiation in hASCs. Our functional study contributes to a better knowledge of molecular mechanisms governing the osteogenic ability of hASCs, and highlights TWIST1 as a potential target to facilitate in vivo bone healing.

Indexed as

AcyltransferasesAnimalsBone Morphogenetic ProteinsCell DifferentiationFibroblast Growth FactorsGene Knockdown TechniquesHumansMaleMAP Kinase Signaling SystemMiceMice, NudeNuclear ProteinsSignal TransductionTissue EngineeringTranscription FactorsTransfectionAcyltransferasesBone Morphogenetic ProteinsFibroblast Growth FactorsNuclear ProteinsTAFAZZIN protein, humantafazzin protein, mouseTranscription FactorsTWIST1 protein, humanTwist1 protein, mouseTwist-Related Protein 1ActivationhASCsOsteogenesisSignalingSilencingTAZTWIST1Upregulation

Identifiers

PMID25446627
PMCPMC5720150
OpenAlexW2142012799

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.