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

June Seok Heo, Seung Gwan Lee, Hyun Ok Kim

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31 Citations (Scopus)


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
Issue number5
Publication statusPublished - 2017 Nov

Bibliographical note

Funding Information:
The present study was supported by Grant HI15C0942 from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea.


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

ASJC Scopus subject areas

  • Genetics


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