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

Heo,June  Seok; Lee,Seung  Gwan; Kim,Hyun  Ok

doi:10.3892/ijmm.2017.3142

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
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Affiliations: Department of Integrated Biomedical and Life Sciences, College of Health Science, Korea University, Seoul 02841; 2Cell Therapy Center, Severance Hospital, Seoul 03722, Republic of Korea, Department of Health and Environmental Science, College of Health Science, Korea University, Seoul 02841, Republic of Korea, Cell Therapy Center, Severance Hospital, Seoul 03722, Republic of Korea
Published online on: September 19, 2017 https://doi.org/10.3892/ijmm.2017.3142
Pages: 1486-1494
Copyright: © Heo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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