Interaction of Nel-like molecule 1 with apoptosis related protein 3 with its influence on human dental pulp cells proliferation and differentiation into odontoblasts

Biochem Biophys Res Commun. 2019 Oct 15;518(2):246-252. doi: 10.1016/j.bbrc.2019.08.042. Epub 2019 Aug 12.

Abstract

Nel-like molecule 1 (Nell-1) is an essential positive regulator of tooth development and odontoblast differentiation. However, its precise mechanism remains undetermined. This study aims to explore the possible receptor or binding protein of Nell-1. Results showed that Nell-1 and Apoptosis related protein 3(APR3) expression levels were high in odontoblasts and inversely correlated. Endogenous Nell-1 co-immunoprecipitated with APR3, and this co-IP was reciprocal. Double immunofluorescence staining revealed that Nell-1 and APR3 colocalized on the nuclear envelope of human dental pulp cells. Nell-1 inhibited the proliferation of these cells co-infected with APR3 through Cyclin D1 downregulation. The interaction of Nell-1 with APR3 stimulated alkaline phosphatase (ALP) activity and promoted the expression and mineralization of DSPP, ALP, OPN, and BSP. The shRNA of APR3 decreased cell differentiation and mineralization. Nell-1 could reciprocally interact with APR3 and stimulate the differentiation and mineralization of human dental pulp cells. Future studies should explore the potential functional connection and the molar mechanism of such interaction.

Keywords: Apoptosis related protein 3; Dental pulp cells; Differentiation; Mineralization; Nel-like protein 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis Regulatory Proteins / metabolism*
  • Calcium-Binding Proteins / metabolism*
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Dental Pulp / cytology*
  • Dental Pulp / metabolism
  • Humans
  • Membrane Transport Proteins
  • Odontoblasts / cytology*
  • Odontoblasts / metabolism
  • Odontogenesis
  • Protein Interaction Maps

Substances

  • ATRAID protein, human
  • Apoptosis Regulatory Proteins
  • Calcium-Binding Proteins
  • Membrane Transport Proteins
  • NELL1 protein, human