The role of Rho-GEF Trio in regulating tooth root development through the p38 MAPK pathway

Exp Cell Res. 2018 Nov 15;372(2):158-167. doi: 10.1016/j.yexcr.2018.09.022. Epub 2018 Sep 27.

Abstract

Trio, the Rho guanine nucleotide exchange factor (Rho-GEF), plays diverse roles in cell migration, cell axon guidance and cytoskeleton reorganization. Conserved during evolution, Trio encodes two guanine nucleotide exchange factor domains (GEFs) and activates small GTPases. The Rho-family small GTPases RhoA and Rac1, which are target molecules of Trio, have been described to engage in craniofacial development and tooth formation. However, the exact role of Trio in tooth development remains elusive. In this study, we generated Wnt1-cre;Triofl/fl mice to address the potential function of Trio in tooth development. Wnt1-cre;Triofl/fl mice showed short root deformity as well as decreased expression of odontogenic makers such as RUNX2, OSX, OCN, and OPN. In vitro, Trio was silenced in human stem cells of dental papilla (SCAPs). Compared with the control group, the proliferation and migration ability in the experimental group was disrupted. After knocking down Trio in SCAPs, the cells showed phenotypes of poor odontogenic differentiation and weak mineralized nodules. To study the underlying mechanism, we investigated the p38 MAPK pathway and found that loss of Trio blocked the cascade transduction of p38 MAPK signaling. In conclusion, we identified Trio as a novel coordinator in regulating root development and clarified its relevant molecular events.

Keywords: Bone modeling; Odontogenesis; Osteogenesis; Trio.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Movement / genetics
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Dental Papilla / growth & development
  • Dental Papilla / metabolism
  • Guanine Nucleotide Exchange Factors / genetics*
  • Humans
  • Mice
  • Neuropeptides / genetics
  • Odontogenesis / genetics*
  • Phosphoproteins / genetics*
  • Protein Binding / genetics
  • Protein Serine-Threonine Kinases / genetics*
  • Signal Transduction / genetics
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Tooth Root / growth & development*
  • Tooth Root / metabolism
  • p38 Mitogen-Activated Protein Kinases / genetics*
  • rac1 GTP-Binding Protein / genetics
  • rho GTP-Binding Proteins / genetics
  • rhoA GTP-Binding Protein

Substances

  • Core Binding Factor Alpha 1 Subunit
  • Guanine Nucleotide Exchange Factors
  • Neuropeptides
  • Phosphoproteins
  • Rac1 protein, mouse
  • Runx2 protein, mouse
  • Trio protein, mouse
  • Protein Serine-Threonine Kinases
  • p38 Mitogen-Activated Protein Kinases
  • RhoA protein, mouse
  • rac1 GTP-Binding Protein
  • rho GTP-Binding Proteins
  • rhoA GTP-Binding Protein