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

Authors
 JUNE SEOK HEO  ;  SEUNG GWAN LEE  ;  HYUN OK KIM 
Citation
 International Journal of Molecular Medicine, Vol.40(5) : 1486-1494, 2017 
Journal Title
 International Journal of Molecular Medicine 
ISSN
 1107-3756 
Issue Date
2017
MeSH
Bone Morphogenetic Protein 2/metabolism ; Cell Differentiation/genetics* ; Cell Survival/genetics ; Cells, Cultured ; Diterpenes, Abietane/pharmacology ; Fetal Blood/cytology ; Gene Expression Regulation, Developmental* ; Homeodomain Proteins/genetics* ; Humans ; Mesenchymal Stromal Cells/cytology* ; Mesenchymal Stromal Cells/metabolism* ; Osteogenesis/genetics* ; RNA Interference ; RNA, Small Interfering/genetics ; Signal Transduction/drug effects ; Transcription Factors/genetics*
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.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/160841
DOI
10.3892/ijmm.2017.3142
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실)
Yonsei Authors
김현옥(Kim, Hyun Ok) ; 허준석(Heo, June Seok)
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