Distal-less homeobox 5 is a master regulator of the osteogenesis of human mesenchymal stem cells

June Seok Heo, Seung Kwan Lee, Hyun Ok Kim

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Mesenchymal stem cells (MSCs) differentiate into multiple lineages and are a promising source of cells for clinical use. Previously, we found that the gene distal-less homeobox 5 (DLX5) is specifically expressed in MSCs with osteogenic potential. Understanding the mechanism of osteogenesis is necessary for successful bone regeneration using MSCs. The aim of this study was to examine the function of the DLX5 gene in MSCs during osteogenesis (bone development). We analyzed the possible association between DLX5 expression and osteogenesis-, chondrogenesis- and adipogenesis-related gene expression in different cells isolated from bone marrow and cord blood. Differentiation capacity was assessed by observing morphological changes, monitoring gene expression patterns, and staining with Von Kossa, safranin O, and Oil Red O. Suppression of DLX5 expression by means of a small interfering RNA (siRNA) downregulated osteogenic markers and reduced the signs of calcium mineralization. Tanshinone IIA is a known small molecule activator of bone morphogenetic protein (BMP) signaling. Here, we report that induction of DLX5 by tanshinone IIA in MSCs enhanced osteogenic differentiation. In addition, we showed that tanshinone IIA (as a mediator of BMP2 signaling) activates runt-related transcription factor 2 (RUNX2) in MSCs and initiates calcium mineralization during osteogenesis. Taken together, these findings indicate that, in MSCs, DLX5 is a master regulator of osteogenesis. Furthermore, tanshinone IIA may be valuable for stem cell-based therapies of certain bone diseases.

Original languageEnglish
Pages (from-to)1486-1494
Number of pages9
JournalInternational Journal of Molecular Medicine
Volume40
Issue number5
DOIs
Publication statusPublished - 2017 Nov 1

Fingerprint

Homeobox Genes
Mesenchymal Stromal Cells
Osteogenesis
Calcium
Chondrogenesis
Adipogenesis
Bone Morphogenetic Proteins
Bone Regeneration
Bone Diseases
Bone Development
Gene Expression Profiling
Cell- and Tissue-Based Therapy
Fetal Blood
Bone Marrow Cells
Small Interfering RNA
Transcription Factors
Stem Cells
Down-Regulation
Staining and Labeling
Gene Expression

Keywords

  • Distal-less homeobox 5
  • Mesenchymal stem cells
  • Osteogenesis
  • Tanshinone IIA

ASJC Scopus subject areas

  • Genetics

Cite this

Distal-less homeobox 5 is a master regulator of the osteogenesis of human mesenchymal stem cells. / Heo, June Seok; Lee, Seung Kwan; Kim, Hyun Ok.

In: International Journal of Molecular Medicine, Vol. 40, No. 5, 01.11.2017, p. 1486-1494.

Research output: Contribution to journalArticle

@article{0c59f48f9a384cf4bc9f8e51ab49070c,
title = "Distal-less homeobox 5 is a master regulator of the osteogenesis of human mesenchymal stem cells",
abstract = "Mesenchymal stem cells (MSCs) differentiate into multiple lineages and are a promising source of cells for clinical use. Previously, we found that the gene distal-less homeobox 5 (DLX5) is specifically expressed in MSCs with osteogenic potential. Understanding the mechanism of osteogenesis is necessary for successful bone regeneration using MSCs. The aim of this study was to examine the function of the DLX5 gene in MSCs during osteogenesis (bone development). We analyzed the possible association between DLX5 expression and osteogenesis-, chondrogenesis- and adipogenesis-related gene expression in different cells isolated from bone marrow and cord blood. Differentiation capacity was assessed by observing morphological changes, monitoring gene expression patterns, and staining with Von Kossa, safranin O, and Oil Red O. Suppression of DLX5 expression by means of a small interfering RNA (siRNA) downregulated osteogenic markers and reduced the signs of calcium mineralization. Tanshinone IIA is a known small molecule activator of bone morphogenetic protein (BMP) signaling. Here, we report that induction of DLX5 by tanshinone IIA in MSCs enhanced osteogenic differentiation. In addition, we showed that tanshinone IIA (as a mediator of BMP2 signaling) activates runt-related transcription factor 2 (RUNX2) in MSCs and initiates calcium mineralization during osteogenesis. Taken together, these findings indicate that, in MSCs, DLX5 is a master regulator of osteogenesis. Furthermore, tanshinone IIA may be valuable for stem cell-based therapies of certain bone diseases.",
keywords = "Distal-less homeobox 5, Mesenchymal stem cells, Osteogenesis, Tanshinone IIA",
author = "Heo, {June Seok} and Lee, {Seung Kwan} and Kim, {Hyun Ok}",
year = "2017",
month = "11",
day = "1",
doi = "10.3892/ijmm.2017.3142",
language = "English",
volume = "40",
pages = "1486--1494",
journal = "International Journal of Molecular Medicine",
issn = "1107-3756",
publisher = "Spandidos Publications",
number = "5",

}

TY - JOUR

T1 - Distal-less homeobox 5 is a master regulator of the osteogenesis of human mesenchymal stem cells

AU - Heo, June Seok

AU - Lee, Seung Kwan

AU - Kim, Hyun Ok

PY - 2017/11/1

Y1 - 2017/11/1

N2 - Mesenchymal stem cells (MSCs) differentiate into multiple lineages and are a promising source of cells for clinical use. Previously, we found that the gene distal-less homeobox 5 (DLX5) is specifically expressed in MSCs with osteogenic potential. Understanding the mechanism of osteogenesis is necessary for successful bone regeneration using MSCs. The aim of this study was to examine the function of the DLX5 gene in MSCs during osteogenesis (bone development). We analyzed the possible association between DLX5 expression and osteogenesis-, chondrogenesis- and adipogenesis-related gene expression in different cells isolated from bone marrow and cord blood. Differentiation capacity was assessed by observing morphological changes, monitoring gene expression patterns, and staining with Von Kossa, safranin O, and Oil Red O. Suppression of DLX5 expression by means of a small interfering RNA (siRNA) downregulated osteogenic markers and reduced the signs of calcium mineralization. Tanshinone IIA is a known small molecule activator of bone morphogenetic protein (BMP) signaling. Here, we report that induction of DLX5 by tanshinone IIA in MSCs enhanced osteogenic differentiation. In addition, we showed that tanshinone IIA (as a mediator of BMP2 signaling) activates runt-related transcription factor 2 (RUNX2) in MSCs and initiates calcium mineralization during osteogenesis. Taken together, these findings indicate that, in MSCs, DLX5 is a master regulator of osteogenesis. Furthermore, tanshinone IIA may be valuable for stem cell-based therapies of certain bone diseases.

AB - Mesenchymal stem cells (MSCs) differentiate into multiple lineages and are a promising source of cells for clinical use. Previously, we found that the gene distal-less homeobox 5 (DLX5) is specifically expressed in MSCs with osteogenic potential. Understanding the mechanism of osteogenesis is necessary for successful bone regeneration using MSCs. The aim of this study was to examine the function of the DLX5 gene in MSCs during osteogenesis (bone development). We analyzed the possible association between DLX5 expression and osteogenesis-, chondrogenesis- and adipogenesis-related gene expression in different cells isolated from bone marrow and cord blood. Differentiation capacity was assessed by observing morphological changes, monitoring gene expression patterns, and staining with Von Kossa, safranin O, and Oil Red O. Suppression of DLX5 expression by means of a small interfering RNA (siRNA) downregulated osteogenic markers and reduced the signs of calcium mineralization. Tanshinone IIA is a known small molecule activator of bone morphogenetic protein (BMP) signaling. Here, we report that induction of DLX5 by tanshinone IIA in MSCs enhanced osteogenic differentiation. In addition, we showed that tanshinone IIA (as a mediator of BMP2 signaling) activates runt-related transcription factor 2 (RUNX2) in MSCs and initiates calcium mineralization during osteogenesis. Taken together, these findings indicate that, in MSCs, DLX5 is a master regulator of osteogenesis. Furthermore, tanshinone IIA may be valuable for stem cell-based therapies of certain bone diseases.

KW - Distal-less homeobox 5

KW - Mesenchymal stem cells

KW - Osteogenesis

KW - Tanshinone IIA

UR - http://www.scopus.com/inward/record.url?scp=85031940976&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85031940976&partnerID=8YFLogxK

U2 - 10.3892/ijmm.2017.3142

DO - 10.3892/ijmm.2017.3142

M3 - Article

C2 - 28949384

AN - SCOPUS:85031940976

VL - 40

SP - 1486

EP - 1494

JO - International Journal of Molecular Medicine

JF - International Journal of Molecular Medicine

SN - 1107-3756

IS - 5

ER -