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Published on: March 15, 2018
mTor plays an important role in odontoblast differentiation
Jin-Koo Kim1, James Baker, Jacques E Nor
1Department of Biology and Materials Sciences, University of Michigan, School of Dentistry, Ann Arbor, Michigan, USA.
Introduction:
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.
Insights
Mammalian target of rapamycin (mTor) pathways influence dental pulp stem cell (SHED) differentiation. Torc1 inhibition restricts dentin formation, while Torc2 inhibition enhances it, suggesting mTor’s role in dental tissue engineering.
Area of Science:
- Biomedical Science
- Stem Cell Biology
- Regenerative Medicine
Background:
- Dentin regeneration mechanisms in dental pulp remain unclear.
- The role of mammalian target of rapamycin (mTor) in dental pulp stem cell (SHED) differentiation and mineralization requires elucidation.
- Investigating mTor complexes (Torc1 and Torc2) is crucial for understanding odontoblast differentiation and extracellular matrix deposition.
Purpose of the Study:
- To determine the effects of mTor signaling on the differentiation and mineralization of SHED.
- To investigate the specific roles of Torc1 and Torc2 in these processes.
- To explore the potential of targeting mTor pathways for dental pulp tissue engineering.
Main Methods:
- Western blot analysis to assess dental differentiation markers in SHED.
- Inhibition of Torc1 (using raptor) and Torc2 (using rictor) complexes.
- Alkaline phosphatase and alizarin red staining to evaluate mineralized matrix deposition.
Main Results:
- Torc1 inhibition significantly reduced dentin sialoprotein synthesis and mineralized matrix deposition.
- Torc2 inhibition enhanced mineralization, an effect dependent on Torc1 activity.
- mTor inhibition via Torc1 or Torc2 modulation impacts SHED differentiation and mineralization.
Conclusions:
- mTor signaling plays a critical role in SHED differentiation and mineralization.
- Torc1 and Torc2 exhibit distinct and interdependent roles in regulating these processes.
- Targeting mTor-mediated protein synthesis pathways offers potential for dental pulp tissue engineering.
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