IPO7 Promotes Odontoblastic Differentiation and Inhibits Osteoblastic Differentiation Through Regulation of RUNX2 Expression and Translocation

Stem Cells. 2022 Nov 29;40(11):1020-1030. doi: 10.1093/stmcls/sxac055.

Abstract

RUNX2, an important transcriptional factor for both odontoblastic and osteoblastic differentiation, is upregulated during osteoblastic differentiation, but downregulated during late odontoblastic differentiation. However, the specific mechanism of the different RUNX2 expression in bone and dentin remains largely unknown. Importin 7 (IPO7), a member of the karyopherin β-superfamily, mediates nucleocytoplasmic transport of proteins. In this study, we found that IPO7 was increasingly expressed from pre-odontoblasts to mature odontoblasts. IPO7 expression was increased with odontoblastic differentiation of mouse dental papilla cells (mDPCs) and knockdown of IPO7-inhibited cell differentiation. While in MC3T3-E1 cells, IPO7 was decreased during osteoblastic differentiation and knockdown of IPO7-promoted cell differentiation. In mPDCs, IPO7 was able to bind with some odontoblastic transcription factors, and imported them into the nucleus, but not with RUNX2. Furthermore, IPO7 inhibited the total RUNX2 expression by promoting HDAC6 nuclear localization during odontoblastic differentiation. However, in MC3T3-E1 cells, IPO7 inhibited the nuclear distribution of RUNX2 but did not affect the total protein level of RUNX2. In conclusion, we found that IPO7 promotes odontoblastic differentiation and inhibits osteoblastic differentiation through regulating RUNX2 expression and translocation differently.

Keywords: RUNX2; importin 7; mouse dental papilla cells (mDPCs); odontoblastic differentiation; osteoblastic differentiation.

MeSH terms

  • Animals
  • Cell Differentiation* / genetics
  • Core Binding Factor Alpha 1 Subunit* / genetics
  • Core Binding Factor Alpha 1 Subunit* / metabolism
  • Dental Pulp / metabolism
  • Extracellular Matrix Proteins / metabolism
  • Gene Expression Regulation
  • Karyopherins* / metabolism
  • Mice
  • Odontoblasts* / cytology
  • Osteoblasts* / cytology
  • Transcription Factors / metabolism

Substances

  • Core Binding Factor Alpha 1 Subunit
  • Extracellular Matrix Proteins
  • Runx2 protein, mouse
  • Transcription Factors
  • Ipo7 protein, mouse
  • Karyopherins