Transforming growth factor-? 1 promotes early odontoblastic differentiation of dental pulp stem cells via activating AKT, Erk1/2 and p38 MAPK pathways

Background/purpose: TGF-01 (Transforming growth factor-01) plays an important role in the regeneration and repair of pulp-dentin complex. However, the biological function of TGF-01 on odontoblastic differentiation remains unclear, mainly due to the processes of differentia-tion were controlled by complex signaling pathways. This study aimed to investigate the signaling pathways involved in regulating the early differentiation of dental pulp stem cells (DPSCs) by TGF-01 and their functional role.Materials and methods: DPSCs were treated with 1 ng/mL TGF-01 and Western blotting was conducted to examine the activation of protein kinase B (AKT), small mothers against decapen-taplegic 3 (Smad3), p38 mitogen-activated protein kinase (p38 MAPK), c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase 1/2 (Erk1/2). DPSCs were exposed to mineral-ization medium contained TGF-01 with/without the specific signaling pathway inhibitors, and early odontogenic differentiation was evaluated by assessing the expression of alkaline phos-phatase (ALP), collagen type 1 alpha 1 (COL1A), dentin matrix protein 1 (DMP-1) and runt -related transcription factor 2 (Runx2).Results: TGF-131 stimulated AKT, Smad3, p38 MAPK, Erk1/2 and JNK phosphorylation in DPSCs within 120 min. TGF-131 enhanced ALP activity and elevated levels of COL1A, DMP-1 and Runx2. LY294002, U0126 and SB203580 attenuated the effect of TGF-131 on DPSCs, however, the SIS3 and SP600125 treated groups had no significant effect.Conclusion: TGF-131 promotes the early stage of odontoblastic differentiation in DPSCs by acti-vating AKT, Erk1/2 and p38 MAPK signaling pathways, but not by Smad3 and JNK. 2022 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).