Regulation of the regenerative activity of dental pulp stem cells from exfoliated deciduous teeth (SHED) of children by TGF-β1 is associated with ALK5/Smad2, TAK1, p38 and MEK/ERK signaling
Journal
Aging
Journal Volume
12
Journal Issue
21
Pages
21253-21272
Date Issued
2020
Author(s)
Chen I.-L.
Chang M.-C.
Lan W.-C.
Yeung S.-Y.
Abstract
Transforming growth factor-β1 (TGF-β1) regulates wound healing/regeneration and aging processes. Dental pulp stem cells from human exfoliated deciduous teeth (SHED) are cell sources for treatment of age-related disorders. We studied the effect of TGF-β1 on SHED and related signaling. SHED were treated with TGF-β1 with/without pretreatment/co-incubation by SB431542, U0126, 5Z-7-oxozeaenol or SB203580. Sircol collagen assay, 3-(4,5-Dimethylthiazol-2-yl)-2,5- diphenyl tetrazolium bromide (MTT) assay, alkaline phosphatase (ALP) assay, RT-PCR, western blotting and PathScan phospho-ELISA were used to measure the effects. We found that SHED expressed ALK1, ALK3, ALK5, TGF-RII, betaglycan and endoglin mRNA. TGF-β1 stimulated p-Smad2, p-TAK1, p-ERK, p-p38 and cyclooxygenase-2 (COX-2) protein expression. It enhanced proliferation and collagen content of SHED that were attenuated by SB431542, 5Z-7-oxozeaenol and SB203580, but not U0126. TGF-β1 (0.5-1 ng/ml) stimulated ALP of SHED, whereas 5-10 ng/ml TGF-β1 suppressed ALP. SB431542 reversed the effects of TGF-β1. However, 5Z-7-oxozeaenol, SB203580 and U0126 only reversed the stimulatory effect of TGF-β1 on ALP. Four inhibitors attenuated TGF-β1-induced COX-2 expression. TGF-β1-stimulated TIMP-1 and N-cadherin was inhibited by SB431542 and 5Z-7-oxozeaenol. These results indicate that TGF-β1 affects SHED by differential regulation of ALK5/Smad2/3, TAK1, p38 and MEK/ERK. TGF-β1 and SHED could potentially be used for tissue engineering/regeneration and treatment of age-related diseases. ? 2020. All Rights Reserved.
SDGs
Other Subjects
MAP kinase kinase kinase 7; mitogen activated protein kinase; mitogen activated protein kinase kinase; mitogen activated protein kinase kinase kinase; mitogen activated protein kinase p38; Smad2 protein; SMAD2 protein, human; Smad3 protein; SMAD3 protein, human; TGFBR1 protein, human; transforming growth factor beta1; cell culture; cell proliferation; cytology; deciduous tooth; drug effect; enzymology; human; metabolism; phosphorylation; regeneration; signal transduction; stem cell; tooth pulp; Cell Proliferation; Cells, Cultured; Dental Pulp; Extracellular Signal-Regulated MAP Kinases; Humans; MAP Kinase Kinase Kinases; Mitogen-Activated Protein Kinase Kinases; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Receptor, Transforming Growth Factor-beta Type I; Regeneration; Signal Transduction; Smad2 Protein; Smad3 Protein; Stem Cells; Tooth, Deciduous; Transforming Growth Factor beta1
Publisher
Impact Journals LLC
Type
journal article