MIR146A inhibits JMJD3 expression and osteogenic differentiation in human mesenchymal stem cells

Jessica M. Huszar; Christopher J. Payne

doi:10.1016/j.febslet.2014.03.057

MIR146A inhibits JMJD3 expression and osteogenic differentiation in human mesenchymal stem cells

Jessica M. Huszar, Christopher J. Payne^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

38 Scopus citations

Abstract

Chromatin remodeling is important for cell differentiation. Histone methyltransferase EZH2 and histone demethylase JMJD3 (KDM6B) modulate levels of histone H3 lysine 27 trimethylation (H3K27me3). Interplay between the two modulators influence lineage specification in stem cells. Here, we identified microRNA MIR146A to be a negative regulator of JMJD3. In the osteogenic differentiation of human mesenchymal stem cells (hMSCs), we observed an upregulation of JMJD3 and a downregulation of MIR146A. Blocking JMJD3 activity in differentiating hMSCs reduced transcript levels of osteogenic gene RUNX2. H3K27me3 levels decreased at the RUNX2 promoter during cell differentiation. Modulation of MIR146A levels in hMSCs altered JMJD3 and RUNX2 expression and affected osteogenic differentiation. We conclude that JMJD3 promotes osteogenesis in differentiating hMSCs, with MIR146A regulating JMJD3.

Original language	English (US)
Pages (from-to)	1850-1856
Number of pages	7
Journal	FEBS Letters
Volume	588
Issue number	9
DOIs	https://doi.org/10.1016/j.febslet.2014.03.057
State	Published - May 2 2014

Keywords

Cell differentiation
Jumonji domain containing 3
MIR146A
MicroRNA
Osteogenesis
Stem cells

ASJC Scopus subject areas

Genetics
Molecular Biology
Biophysics
Structural Biology
Biochemistry
Cell Biology

Access to Document

10.1016/j.febslet.2014.03.057

Cite this

@article{9277647ce53d48988396c9ce9be03869,

title = "MIR146A inhibits JMJD3 expression and osteogenic differentiation in human mesenchymal stem cells",

abstract = "Chromatin remodeling is important for cell differentiation. Histone methyltransferase EZH2 and histone demethylase JMJD3 (KDM6B) modulate levels of histone H3 lysine 27 trimethylation (H3K27me3). Interplay between the two modulators influence lineage specification in stem cells. Here, we identified microRNA MIR146A to be a negative regulator of JMJD3. In the osteogenic differentiation of human mesenchymal stem cells (hMSCs), we observed an upregulation of JMJD3 and a downregulation of MIR146A. Blocking JMJD3 activity in differentiating hMSCs reduced transcript levels of osteogenic gene RUNX2. H3K27me3 levels decreased at the RUNX2 promoter during cell differentiation. Modulation of MIR146A levels in hMSCs altered JMJD3 and RUNX2 expression and affected osteogenic differentiation. We conclude that JMJD3 promotes osteogenesis in differentiating hMSCs, with MIR146A regulating JMJD3.",

keywords = "Cell differentiation, Jumonji domain containing 3, MIR146A, MicroRNA, Osteogenesis, Stem cells",

author = "Huszar, {Jessica M.} and Payne, {Christopher J.}",

note = "Funding Information: The authors thank Kristin Kalita for her contribution towards identifying MIR146A as a target of JMJD3 in preliminary experiments, and Dr. Jenny Kerschner for her careful review of the manuscript. We gratefully acknowledge the Children{\textquoteright}s Research Fund of the Ann & Robert H. Lurie Children{\textquoteright}s Hospital of Chicago Research Center for its generous financial support. C.J.P. is the recipient of an NIH Pathway-to-Independence Award from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R00 HD055330). ",

year = "2014",

month = may,

day = "2",

doi = "10.1016/j.febslet.2014.03.057",

language = "English (US)",

volume = "588",

pages = "1850--1856",

journal = "FEBS Letters",

issn = "0014-5793",

publisher = "Elsevier",

number = "9",

}

TY - JOUR

T1 - MIR146A inhibits JMJD3 expression and osteogenic differentiation in human mesenchymal stem cells

AU - Huszar, Jessica M.

AU - Payne, Christopher J.

N1 - Funding Information: The authors thank Kristin Kalita for her contribution towards identifying MIR146A as a target of JMJD3 in preliminary experiments, and Dr. Jenny Kerschner for her careful review of the manuscript. We gratefully acknowledge the Children’s Research Fund of the Ann & Robert H. Lurie Children’s Hospital of Chicago Research Center for its generous financial support. C.J.P. is the recipient of an NIH Pathway-to-Independence Award from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R00 HD055330).

PY - 2014/5/2

Y1 - 2014/5/2

N2 - Chromatin remodeling is important for cell differentiation. Histone methyltransferase EZH2 and histone demethylase JMJD3 (KDM6B) modulate levels of histone H3 lysine 27 trimethylation (H3K27me3). Interplay between the two modulators influence lineage specification in stem cells. Here, we identified microRNA MIR146A to be a negative regulator of JMJD3. In the osteogenic differentiation of human mesenchymal stem cells (hMSCs), we observed an upregulation of JMJD3 and a downregulation of MIR146A. Blocking JMJD3 activity in differentiating hMSCs reduced transcript levels of osteogenic gene RUNX2. H3K27me3 levels decreased at the RUNX2 promoter during cell differentiation. Modulation of MIR146A levels in hMSCs altered JMJD3 and RUNX2 expression and affected osteogenic differentiation. We conclude that JMJD3 promotes osteogenesis in differentiating hMSCs, with MIR146A regulating JMJD3.

AB - Chromatin remodeling is important for cell differentiation. Histone methyltransferase EZH2 and histone demethylase JMJD3 (KDM6B) modulate levels of histone H3 lysine 27 trimethylation (H3K27me3). Interplay between the two modulators influence lineage specification in stem cells. Here, we identified microRNA MIR146A to be a negative regulator of JMJD3. In the osteogenic differentiation of human mesenchymal stem cells (hMSCs), we observed an upregulation of JMJD3 and a downregulation of MIR146A. Blocking JMJD3 activity in differentiating hMSCs reduced transcript levels of osteogenic gene RUNX2. H3K27me3 levels decreased at the RUNX2 promoter during cell differentiation. Modulation of MIR146A levels in hMSCs altered JMJD3 and RUNX2 expression and affected osteogenic differentiation. We conclude that JMJD3 promotes osteogenesis in differentiating hMSCs, with MIR146A regulating JMJD3.

KW - Cell differentiation

KW - Jumonji domain containing 3

KW - MIR146A

KW - MicroRNA

KW - Osteogenesis

KW - Stem cells

UR - http://www.scopus.com/inward/record.url?scp=84899658053&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84899658053&partnerID=8YFLogxK

U2 - 10.1016/j.febslet.2014.03.057

DO - 10.1016/j.febslet.2014.03.057

M3 - Article

C2 - 24726732

AN - SCOPUS:84899658053

SN - 0014-5793

VL - 588

SP - 1850

EP - 1856

JO - FEBS Letters

JF - FEBS Letters

IS - 9

ER -

MIR146A inhibits JMJD3 expression and osteogenic differentiation in human mesenchymal stem cells

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this