Role of Special AT-Rich Sequence-Binding Protein 2 in the Osteogenesis of Human Dental Mesenchymal Stem Cells

Stem Cells Dev. 2020 Aug;29(16):1059-1072. doi: 10.1089/scd.2020.0013. Epub 2020 Jun 25.

Abstract

Dental mesenchymal stem cells (MSCs) are recognized as a critical factor in repair of defective craniofacial bone owing to the multiple differentiation potential, the ability to regenerate distinct tissues, and the advantage that they can be easily obtained by relatively noninvasive procedures. Special AT-rich sequence-binding protein 2 (SATB2) is a nuclear matrix protein, involved in chromatin remodeling and transcriptional regulation, and has been reported to be as a positive regulator of osteoblast differentiation, bone formation, and bone regeneration in MSCs. In this study, we systematically investigated the capability of SATB2 to promote the osteogenic differentiation of periodontal ligament stem cells (PDLSCs), dental pulp stem cells (DPSCs), and stem cells from human exfoliated deciduous teeth (SHED). RNA-seq analysis and quantitative real-time PCR (RT-PCR) revealed that genes regulating osteogenic differentiation were differentially expressed among three cell types and SATB2 was found to be expressed at a relatively high level. When the three cell types overexpressed SATB2 with AdSATB2 infection, alkaline phosphatase (ALP) staining, ALP activity, Alizarin Red S staining, and quantification tended to increase with an increasing infection rate. It showed opposite results after infection with AdsiSATB2. RNA-seq analysis indicated that the expression of downstream osteogenic genes was affected by AdSATB2 infection and quantitative RT-PCR confirmed that nine osteogenic genes (Spp1, Sema7a, Atf4, Ibsp, Col1a1, Sp7, Igfbp3, Dlx3, and Alpl) were upregulated, to various extents, following SATB2 overexpression. In addition, quantitative PCR results indicated that SATB2 affected the expression of MSC markers. These results suggested an important role of SATB2 in the osteogenesis of PDLSCs, DPSCs, and SHED. Further research is warranted to investigate SATB2-mediated regulation of osteogenic differentiation and to evaluate the therapeutic use of SATB2 for the regeneration of defective craniofacial bone tissue.

Keywords: dental mesenchymal stem cells; osteogenesis; special AT-rich sequence-binding protein 2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Biomarkers / metabolism
  • Cell Differentiation / genetics
  • Dental Pulp / cytology
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Silencing
  • Humans
  • Male
  • Matrix Attachment Region Binding Proteins / genetics
  • Matrix Attachment Region Binding Proteins / metabolism*
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism*
  • Osteogenesis* / genetics
  • Periodontal Ligament / cytology
  • Reproducibility of Results
  • Tooth / cytology*
  • Tooth Exfoliation
  • Tooth, Deciduous / cytology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Biomarkers
  • Matrix Attachment Region Binding Proteins
  • SATB2 protein, human
  • Transcription Factors