title: mTor plays an important role in odontoblast differentiation.
abstract: BACKGROUND
  Signaling pathways responsible for dentin regeneration in a dental pulp are not fully understood. In this study, we determined the effects of the mammalian target of rapamycin (mTor) on the differentiation and mineralization of dental pulp stem cells. We hypothesized that the two known mTor complexes Torc1 and Torc 2 play pivotal roles in the differentiation of odontoblasts and that they modulate deposition of a mineralized extracellular matrix. Therefore, we investigated the effects of Torc1 and Torc 2 signaling on the differentiation and mineralization of stem cells from human exfoliated deciduous teeth (SHED).
  
  
  METHODS
  We used Western blot analysis to examine the expression of markers of dental differentiation in SHED (+/-) inhibition of either Torc1 or Torc 2 complex proteins raptor or rictor, respectively. In addition, the deposition of a mineralized matrix was determined under these conditions via alkaline phosphatase and alizarin red staining.
  
  
  RESULTS
  Results show that the inhibition of Torc 1, via reduced expression of either raptor or mTor, severely restricts the synthesis of dentin sialoprotein and inhibits deposition of a mineralized matrix. Inhibition of Torc 2, via reduction of rictor, has the opposite effect, enhancing mineralization. This latter effect disappears when both rictor and mTor are inhibited, showing that the Torc 2 effect is Torc 1 dependent.
  
  
  CONCLUSIONS
  These results strongly suggest an important role for mTor in dental pulp stem cell differentiation and provide evidence that the mechanisms involved in protein synthesis could prove an interesting target for dental pulp tissue engineering.
authors.affiliation: Department of Biology and Materials Sciences, University of Michigan, School of Dentistry, Ann Arbor, Michigan, USA.
authors.forename: Jin-Koo
authors.initials: JK
authors.lastname: Kim
authors.forename: James
authors.initials: J
authors.lastname: Baker
authors.forename: Jacques E
authors.initials: JE
authors.lastname: Nor
authors.forename: Elliott E
authors.initials: EE
authors.lastname: Hill
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000502:physiology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis; D006801:Humans; D009804:Odontoblasts / Q000166:cytology* / Q000378:metabolism; D010750:Phosphoproteins / Q000096:biosynthesis; D014176:Protein Biosynthesis / Q000502:physiology; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D000076223:Regulatory-Associated Protein of mTOR; D012795:Sialoglycoproteins / Q000096:biosynthesis; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000502:physiology*; D014074:Tooth Calcification / Q000187:drug effects / Q000502:physiology; D014094:Tooth, Deciduous / Q000166:cytology*; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000502:physiology; D000099311:Dentin Sialophosphoprotein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000900:Anti-Bacterial Agents; D002352:Carrier Proteins; D016326:Extracellular Matrix Proteins; D010750:Phosphoproteins; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D000076223:Regulatory-Associated Protein of mTOR; D012795:Sialoglycoproteins; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors; D000099311:Dentin Sialophosphoprotein; C500984:CRTC1 protein, human; C493245:CRTC2 protein, human; C492571:RICTOR protein, human; C463659:RPTOR protein, human; C546842:MTOR protein, human