title: Mechanical forces induce odontoblastic differentiation of mesenchymal stem cells on three-dimensional biomimetic scaffolds.
abstract: The mechanical induction of cell differentiation is well known. However, the effect of mechanical compression on odontoblastic differentiation remains to be elucidated. Thus, we first determined the optimal conditions for the induction of human dental pulp stem cells (hDPSCs) into odontoblastic differentiation in response to mechanical compression of three-dimensional (3D) scaffolds with dentinal tubule-like pores. The odontoblastic differentiation was evaluated by gene expression and confocal laser microscopy. The optimal conditions, which were: cell density, 4.0 × 105cells/cm2; compression magnitude, 19.6 kPa; and loading time, 9 h, significantly increased expression of the odontoblast-specific markers dentine sialophosphoprotein (DSPP) and enamelysin and enhanced the elongation of cellular processes into the pores of the membrane, a typical morphological feature of odontoblasts. In addition, upregulation of bone morphogenetic protein 7 (BMP7) and wingless-type MMTV integration site family member 10a (Wnt10a) was observed. Moreover, the phosphorylation levels of mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 were also enhanced by mechanical compression, indicating the involvement of the MAPK signalling pathway. It is noteworthy that human mesenchymal stem cells (MSCs) derived from bone marrow and amnion also differentiated into odontoblasts in response to the optimal mechanical compression, demonstrating the importance of the physical structure of the scaffold in odontoblastic differentiation. Thus, odontoblastic differentiation of hDPSCs is promoted by optimal mechanical compression through the MAPK signalling pathway and expression of the BMP7 and Wnt10a genes. The 3D biomimetic scaffolds with dentinal tubule-like pores were critical for the odontoblastic differentiation of MSCs induced by mechanical compression. Copyright © 2014 John Wiley & Sons, Ltd.
authors.affiliation: Department of Dental Regenerative Medicine, Centre of Advanced Medicine for Dental and Oral Diseases, National Centre for Geriatrics and Gerontology, Aichi, Japan.|Division of Orthodontics and Dentofacial Orthopaedics, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Miyagi, Japan.
authors.forename: Shunro
authors.initials: S
authors.lastname: Miyashita
authors.affiliation: Orodental Genetics Department, National Research Centre, Cairo, Egypt.
authors.forename: Nermeen El Motaz Bellah
authors.initials: NE
authors.lastname: Ahmed
authors.affiliation: Department of Dental Regenerative Medicine, Centre of Advanced Medicine for Dental and Oral Diseases, National Centre for Geriatrics and Gerontology, Aichi, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Murakami
authors.affiliation: Department of Dental Regenerative Medicine, Centre of Advanced Medicine for Dental and Oral Diseases, National Centre for Geriatrics and Gerontology, Aichi, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Iohara
authors.affiliation: Department of Urology, Nagoya University Graduate School of Medicine, Japan.
authors.forename: Tokunori
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Aichi-Gakuin University, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Horibe
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Aichi-Gakuin University, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kurita
authors.affiliation: Division of Orthodontics and Dentofacial Orthopaedics, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Miyagi, Japan.
authors.forename: Teruko
authors.initials: T
authors.lastname: Takano-Yamamoto
authors.affiliation: Department of Dental Regenerative Medicine, Centre of Advanced Medicine for Dental and Oral Diseases, National Centre for Geriatrics and Gerontology, Aichi, Japan.
authors.forename: Misako
authors.initials: M
authors.lastname: Nakashima
mesh_terms: D000293:Adolescent; D000328:Adult; D032701:Biomimetics; D055419:Bone Morphogenetic Protein 7 / Q000378:metabolism; D002454:Cell Differentiation; D019245:Compressive Strength; D016207:Cytokines / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D020935:MAP Kinase Signaling System; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D018613:Microscopy, Confocal; D008963:Molar / Q000473:pathology; D009804:Odontoblasts / Q000166:cytology*; D010750:Phosphoproteins / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000378:metabolism; D013314:Stress, Mechanical; D054457:Tissue Scaffolds; D055815:Young Adult; D000099311:Dentin Sialophosphoprotein
chemical_list: D055419:Bone Morphogenetic Protein 7; D016207:Cytokines; D016326:Extracellular Matrix Proteins; D036341:Intercellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein; C525820:bmp7 protein, mouse
keywords: dental pulp stem cells; dentinal tubules; mechanical compression; mitogen-activated protein kinase signalling pathway; odontoblastic differentiation; three-dimensional scaffold