MAPK mediates Hsp25 signaling in incisor development

Histochem Cell Biol. 2009 May;131(5):593-603. doi: 10.1007/s00418-009-0568-2. Epub 2009 Feb 19.


Rodent incisors are continuously growing teeth that include all stages of amelogenesis. Understanding amelogenesis requires investigations of the genes and their gene products control the ameloblast phenotype. One of the mechanisms related to tooth differentiation is mitogen-activated protein kinase (MAPK) signaling. The extracellular-signal regulated kinase (ERK)/mitogen-activated protein kinase kinase (MEK) cascade is associated with mechanisms that control the cell cycle and cell survival. However, the roles of cascades in incisor development remain to be determined. In this study, we investigated incisor development and growth in the mouse based on MAPK signaling. Moreover, heat-shock protein (Hsp)-25 is well known to be a useful marker of odontoblast differentiation. We used anisomycin (a protein-synthesis inhibitor that activates MAPKs) and U0126 (a MAPK inhibitor that blocks ERK1/2 phosphorylation) to examine the role of MAPKs in Hsp25 signaling in the development of the mouse incisor. We performed immunohistochemistry and in vitro culture using incisor tooth germ, and found that phospho-ERK (pERK), pMEK, and Hsp25 localized in developing incisor ameloblasts and anisomycin failed to produce incisor development. In addition, Western blotting results showed that anisomycin stimulated the phosphorylation of ERK, MEK, and Hsp25, and that some of these proteins were blocked by the U0126. These findings suggest that MAPK signals play important roles in incisor formation, differentiation, and development by mediating Hsp25 signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ameloblasts / cytology
  • Ameloblasts / drug effects
  • Ameloblasts / metabolism*
  • Animals
  • Anisomycin / pharmacology
  • Butadienes / pharmacology
  • Cell Line
  • Extracellular Signal-Regulated MAP Kinases / drug effects
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Heat-Shock Proteins / drug effects
  • Heat-Shock Proteins / metabolism*
  • Incisor / drug effects
  • Incisor / growth & development*
  • Incisor / metabolism
  • Ki-67 Antigen / drug effects
  • Ki-67 Antigen / metabolism
  • MAP Kinase Kinase Kinases / drug effects
  • MAP Kinase Kinase Kinases / metabolism*
  • Mice
  • Mice, Inbred ICR
  • Neoplasm Proteins / drug effects
  • Neoplasm Proteins / metabolism*
  • Nitriles / pharmacology
  • Organ Culture Techniques
  • Rats
  • Signal Transduction / drug effects
  • Signal Transduction / physiology


  • Butadienes
  • Heat-Shock Proteins
  • Hsbp1 protein, mouse
  • Ki-67 Antigen
  • Neoplasm Proteins
  • Nitriles
  • U 0126
  • Anisomycin
  • Extracellular Signal-Regulated MAP Kinases
  • MAP Kinase Kinase Kinases