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.
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.
Authors: Rasha N Alotaibi; Brian J Howe; Lina M Moreno Uribe; Carla Sanchez; Frederic W B Deleyiannis; Carmencita Padilla; Fernando A Poletta; Ieda M Orioli; Carmen J Buxó; George L Wehby; Alexandre R Vieira; Jeffrey Murray; Consuelo Valencia-Ramírez; Claudia P Restrepo Muñeton; Ross E Long; John R Shaffer; Steven E Reis; Seth M Weinberg; Katherine Neiswanger; Daniel W McNeil; Mary L Marazita Journal: Hum Hered Date: 2022-02-16 Impact factor: 1.455
Authors: Hongli Sun; Jin Koo Kim; Richard Mortensen; Lorraine P Mutyaba; Kurt D Hankenson; Paul H Krebsbach Journal: Stem Cells Date: 2013-10 Impact factor: 6.277
Authors: Mariana Bezamat; Kathleen Deeley; Shahryar Khaliq; Ariadne Letra; Rafaela Scariot; Renato M Silva; Megan L Weber; Diego G Bussaneli; Paula C Trevilatto; Alejandro J Almarza; Hongjiao Ouyang; Alexandre R Vieira Journal: Caries Res Date: 2018-09-11 Impact factor: 4.056