Mechanical stress promotes odontoblastic differentiation via the heme oxygenase-1 pathway in human dental pulp cell line

Aims: Although hemeoxygenase-1 (HO-1) is involved in osteoblastic differentiation. the HO-1-a nd odontoblastic differentiation-inducing effects of mechanical stress (MS) have not been clarified in human dental pulp cells (HDPCs). In this study, we examined the effects of MS on the odontoblastic differentiation of immortalized HDPCs and on the primary intracellular signaling pathways, including the HO-1 pathway, implicated in this differentiation. Main methods: A Flexercell strain unit was used to generate cyclic tensile strain in HDPCs. Expressions of mRNAs encoding HO-1 and HDPC differentiation markers, such as osteopontin (OPN), bone sialoprotein (BSP), dentin sialophosphoprotein (DSPP), and dentin matrix-protein-1 (DMP-1), were evaluated using the reverse transcription-polymerase chain reaction. Expression of the NF-E2-related transcription factor 2 (Nrf2) protein was analyzed by Western blotting. Key findings: MS significantly increased the expression of HO-1, OPN, BSP, DSPP, and DMP-1 mRNAs in HDPCs. HO-1 silencing and inhibitors of HO-1, p38 MAPK ERK, phosphoinositide 3-kinase, and nuclear factor-kappa B (NF-kappa B) all attenuated MS-stimulated differentiation. The MS-induced nuclear translocation of Nrf2 was suppressed by inhibitors of PI3K and NF-kappa B. Significance: Collectively, these results provide the first evidence that MS stimulates odontoblastic differentiation of HDPCs via modulation of the Nrf2-mediated HO-1 pathway. (C) 2009 Elsevier Inc. All rights reserved.