Evidence map›Paper›PMID 29280310›Full record

ArticleStem cells translational medicine2018

Osteogenic Stimulation of Human Adipose-Derived Mesenchymal Stem Cells Using a Fungal Metabolite That Suppresses the Polycomb Group Protein EZH2.

Rebekah M Samsonraj, Amel Dudakovic, Bushra Manzar, Buer Sen, Allan B Dietz, Simon M Cool, Janet Rubin, Andre J van Wijnen

Open access · goldAbstract read
In one paragraph

Article in Stem cells translational medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.2field-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

25 citing papers in PubMed, 43 citations in OpenAlex.

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  16. β-Catenin Preserves the Stem State of Murine Bone Marrow Stromal Cells Through Activation of EZH2.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2020
    Article
  17. Article
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  19. Article
  20. Gene regulation through dynamic actin control of nuclear structure.Experimental biology and medicine (Maywood, N.J.) · 2019
    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 4 institutions in 2 countries.

Rebekah M SamsonrajDepartment of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota, USA.ORCID 0000-0001-8804-8284
Amel DudakovicDepartment of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota, USA.
Bushra ManzarDepartment of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota, USA.
Buer SenDepartment of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA.
Allan B DietzDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Simon M CoolGlycotherapeutics Group, Institute of Medical Biology, Agency for Science, Technology and Research (A*STAR), Singapore.ORCID 0000-0001-8543-3056
Janet RubinDepartment of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA.
Andre J van WijnenDepartment of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota, USA.ORCID 0000-0002-4458-0946
Mayo Clinic · USMayo Clinic in Florida · USUniversity of North Carolina at Chapel Hill · USInstitute of Medical Biology · SG

Funding

Molecular Control of Bone FormationR01AR049069 · NIAMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI WESTENDORF, JENNIFER J · 2003 to 2021
$5.8M
Mechanical regulation of cytoskeleton guides beta-catenin effect on MSC fateR01AR066616 · NIAMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI RUBIN, JANET E · 2015 to 2019
$1.7M
Mechanical Control of Mesenchymal Stem Cell Lineage AllocationR01AR056655 · NIAMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI RUBIN, JANET E · 2010 to 2014
$1.4M
Epigenetic control of osteoblast differentiationF32AR066508 · NIAMS · MAYO CLINIC ROCHESTER · PI DUDAKOVIC, AMEL · 2015 to 2017
$185k
NIAMS NIH HHS F32 AR066508NIAMS NIH HHS R01 AR049069NIAMS NIH HHS R01 AR056655NIAMS NIH HHS R01 AR066616
6 · The paper itself

Abstract

Strategies for musculoskeletal tissue regeneration apply adult mesenchymal stem/stromal cells (MSCs) that can be sourced from bone marrow- and lipo-aspirates. Adipose tissue-derived MSCs are more easily harvested in the large quantities required for skeletal tissue-engineering approaches, but are generally considered to be less osteogenic than bone marrow MSCs. Therefore, we tested a new molecular strategy to improve their osteogenic lineage-differentiation potential using the fungal metabolite cytochalasin D (CytoD). We show that CytoD, which may function by redistributing the intracellular location of β-actin (ACTB), is a potent osteogenic stimulant as reflected by significant increases in alkaline phosphatase activity, extracellular matrix mineralization, and osteoblast-related gene expression (e.g., RUNX2, ALPL, SPARC, and TGFB3). RNA sequencing analyses of MSCs revealed that acute CytoD treatment (24 hours) stimulates a broad program of osteogenic biomarkers and epigenetic regulators. CytoD decreases mRNA and protein levels of the Polycomb chromatin regulator Enhancer of Zeste Homolog 2 (EZH2), which controls heterochromatin formation by mediating trimethylation of histone 3 lysine 27 (H3K27me3). Reduced EZH2 expression decreases cellular H3K27me3 marks indicating a global reduction in heterochromatin. We conclude that CytoD is an effective osteogenic stimulant that mechanistically functions by blocking both cytoplasmic actin polymerization and gene-suppressive epigenetic mechanisms required for the acquisition of the osteogenic phenotype in adipose tissue-derived MSCs. This finding supports the use of CytoD in advancing the osteogenic potential of MSCs in skeletal regenerative strategies. Stem Cells Translational Medicine 2018;7:197-209.

Indexed as

Adipose TissueCell DifferentiationCells, CulturedCytochalasin DEnhancer of Zeste Homolog 2 ProteinEpigenesis, GeneticFungiHistonesHumansMesenchymal Stem CellsOsteoblastsOsteogenesisTissue EngineeringCytochalasin DEnhancer of Zeste Homolog 2 ProteinEZH2 protein, humanHistonesAdipose stem cellsBoneEpigeneticsMesenchymal stem cellsTissue regeneration

Identifiers

PMID29280310
PMCPMC5788881
OpenAlexW2777105378

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.