Special AT-rich sequence-binding protein 2 (Satb2) synergizes with Bmp9 and is essential for osteo/odontogenic differentiation of mouse incisor mesenchymal stem cells

Cell Prolif. 2021 Apr;54(4):e13016. doi: 10.1111/cpr.13016. Epub 2021 Mar 4.

Abstract

Objectives: Mouse incisor mesenchymal stem cells (MSCs) have self-renewal ability and osteo/odontogenic differentiation potential. However, the mechanism controlling the continuous self-renewal and osteo/odontogenic differentiation of mouse incisor MSCs remains unclear. Special AT-rich sequence-binding protein 2 (SATB2) positively regulates craniofacial patterning, bone development and regeneration, whereas SATB2 deletion or mutation leads to craniomaxillofacial dysplasia and delayed tooth and root development, similar to bone morphogenetic protein (BMP) loss-of-function phenotypes. However, the detailed mechanism underlying the SATB2 role in odontogenic MSCs is poorly understood. The aim of this study was to investigate whether SATB2 can regulate self-renewal and osteo/odontogenic differentiation of odontogenic MSCs.

Materials and methods: Satb2 expression was detected in the rapidly renewing mouse incisor mesenchyme by immunofluorescence staining, quantitative RT-PCR and Western blot analysis. Ad-Satb2 and Ad-siSatb2 were constructed to evaluate the effect of Satb2 on odontogenic MSCs self-renewal and osteo/odontogenic differentiation properties and the potential role of Satb2 with the osteogenic factor bone morphogenetic protein 9 (Bmp9) in vitro and in vivo.

Results: Satb2 was found to be expressed in mesenchymal cells and pre-odontoblasts/odontoblasts. We further discovered that Satb2 effectively enhances mouse incisor MSCs self-renewal. Satb2 acted synergistically with the potent osteogenic factor Bmp9 in inducing osteo/odontogenic differentiation of mouse incisor MSCs in vitro and in vivo.

Conclusions: Satb2 promotes self-renewal and osteo/odontogenic differentiation of mouse incisor MSCs. Thus, Satb2 can cooperate with Bmp9 as a new efficacious bio-factor for osteogenic regeneration and tooth engineering.

Keywords: Bmp9; Satb2; bone; mesenchymal stem cells; odontogenic differentiation; osteo; tooth.

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Bone Regeneration
  • Cell Adhesion
  • Cell Differentiation*
  • Cell Line
  • Cell Proliferation
  • Cell Self Renewal
  • Genetic Vectors / genetics
  • Genetic Vectors / metabolism
  • Growth Differentiation Factor 2 / genetics
  • Growth Differentiation Factor 2 / metabolism*
  • Hydrogels / chemistry
  • Incisor / cytology
  • Matrix Attachment Region Binding Proteins / antagonists & inhibitors
  • Matrix Attachment Region Binding Proteins / genetics
  • Matrix Attachment Region Binding Proteins / metabolism*
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Odontoblasts / cytology*
  • Odontoblasts / metabolism
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Tissue Scaffolds / chemistry
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Gdf2 protein, mouse
  • Growth Differentiation Factor 2
  • Hydrogels
  • Matrix Attachment Region Binding Proteins
  • RNA, Small Interfering
  • SATB2 protein, mouse
  • Transcription Factors